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IMDELLTRA® SIGNIFICANTLY REDUCED RISK OF DEATH BY 40% IN SMALL CELL LUNG CANCER PATIENTS
Breakthrough Second-Line Treatment Demonstrated Survival Advantage over Standard-of-Care Chemotherapy Late-Breaking Data Presented at ASCO 2025 and Simultaneously Published in The New England Journal of Medicine THOUSAND OAKS, Calif., June 2, 2025 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced new interim results from the global Phase 3 DeLLphi-304 trial showing IMDELLTRA® (tarlatamab-dlle) reduced the risk of death by 40% and significantly extended median overall survival (OS) by more than five months compared to standard-of-care (SOC) chemotherapy in patients with small cell lung cancer (SCLC) who progressed on or after one line of platinum-based chemotherapy (median OS: 13.6 vs 8.3 months; hazard ratio [HR], 0.60; 95% confidence interval [CI]: 0.47, 0.77; P < 0.001). The results will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (LBA8008) and have been published in The New England Journal of Medicine. "Small cell lung cancer is an extraordinarily aggressive and difficult-to-treat disease, and those living with SCLC often experience limited benefit with first line treatment," said Jay Bradner, M.D., executive vice president, Research and Development, at Amgen. "These data underscore IMDELLTRA's potential to transform patient outcomes and the small cell lung cancer treatment paradigm." At the planned interim analysis, DeLLphi-304 met its primary OS endpoint and key secondary progression-free survival (PFS) endpoint. Additionally, IMDELLTRA significantly improved patient-reported outcomes (PRO) for cancer-related symptoms of dyspnea and cough compared to the control arm. "The data from DeLLphi-304 mark a major milestone for people with relapsed small cell lung cancer. Tarlatamab is associated with significant improvements in both overall and progression-free survival over standard chemotherapy in patients with recurrent or progressive disease," said Charles Rudin, M.D., Ph.D., deputy director, Memorial Sloan Kettering Cancer Center. "This study also provides confirmatory data on management of potential toxicities associated with bispecific T-cell engager therapies in a large patient cohort, which is crucial to continuing to improve the experience of patients treated with these medicines." At a median follow-up of 11.2 months for IMDELLTRA and 11.7 months for the control arm, data from the global Phase 3 DeLLphi-304 clinical trial showed a median OS of 13.6 months with IMDELLTRA compared to 8.3 months with local SOC chemotherapy (HR, 0.60; 95% CI: 0.47, 0.77; P < 0.001). Median PFS was statistically significantly improved for IMDELLTRA compared to local SOC chemotherapy (median PFS: 4.2 vs 3.7 months; HR, 0.71; 95% CI: 0.59, 0.86; P < 0.001). The safety profile for IMDELLTRA in DeLLphi-304 was consistent with its known profile. In DeLLphi-304, lower rates of grade 3 or higher treatment-related adverse events (TRAEs) occurred with IMDELLTRA versus the control arm (27% vs 62%) and discontinuations due to TRAEs were lower with IMDELLTRA compared to the control arm (3% vs 6%). The most common grade 3 or greater TRAEs were neutropenia (4%) and lymphopenia (4%) with IMDELLTRA and anemia (28%) and neutropenia (22%) with local SOC chemotherapy. Cytokine release syndrome (CRS) with IMDELLTRA primarily occurred after receipt of one of the first two doses and was primarily low grade (42% Grade 1; 13% Grade 2; 1% Grade 3) and manageable. No Grade 4 or Grade 5 CRS events were reported. CRS profiles following the first two doses of IMDELLTRA, including incidence, severity, outcome, time to intervention and time to resolution, were similar among patients who were monitored for 6 to 8 hours (n=43) and those who were monitored for 48 hours (n=209). DeLLphi-304 is a global Phase 3, randomized, controlled, open-label clinical trial evaluating the efficacy and safety of IMDELLTRA as a treatment for patients living with SCLC who progressed on or after a single line of platinum-based chemotherapy.1 Five hundred and nine patients were randomized to receive either IMDELLTRA or local SOC chemotherapy (topotecan in all countries except Japan; lurbinectedin in the U.S., Canada, Australia, Singapore, Korea; and amrubicin in Japan).1,2 The primary outcome measure of the trial is OS.1 Key secondary outcome measures include PFS and PROs including disease-related symptoms, physical function and quality of life.1 DeLLphi-304 is intended to serve as the confirmatory trial for IMDELLTRA's accelerated approval for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. About IMDELLTRA® (tarlatamab-dlle)IMDELLTRA is a first-in-class targeted immunotherapy engineered by Amgen researchers to bind to both DLL3 on tumor cells and CD3 on T cells, thereby activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.3,4 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.5,6 IMDELLTRA® (tarlatamab-dlle) U.S. IndicationIMDELLTRA® (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). About Small Cell Lung Cancer (SCLC)SCLC is one of the most aggressive and devastating solid tumor malignancies, with a 5-10% five-year relative survival rate across all stages combined.7 SCLC comprises about 15% of the more than 2.4 million patients diagnosed with lung cancer worldwide each year.8-10 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.9 About Tarlatamab Clinical TrialsAmgen's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens, including in both earlier stages of SCLC and earlier lines of treatment. Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard-of-care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 study comparing tarlatamab monotherapy with standard-of-care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 study comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 study of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; DeLLphi-308, a Phase 1b study evaluating subcutaneous tarlatamab in second line or later ES-SCLC; DeLLphi-309, a Phase 2 study evaluating alternative intravenous dosing regimens with tarlatamab in second-line ES-SCLC; DeLLphi-310, a Phase 1b study of tarlatamab in combination with YL201 with or without anti-programmed death ligand 1 (PD-L1) in patients with ES-SCLC; and DeLLphi-312, a Phase 3 study evaluating tarlatamab as an induction and maintenance therapy in first-line treatment of ES-SCLC in combination with carboplatin, etoposide, and durvalumab.11 For more information, please visit About Amgen Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization. For more information, visit and follow Amgen on X, LinkedIn, Instagram, YouTube and Threads. IMDELLTRA® (tarlatamab-dlle) Important Safety Information (USPI) WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Initiate treatment with IMDELLTRA® using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA® until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA®. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA® until ICANS resolves or permanently discontinue based on severity. WARNINGS AND PRECAUTIONS Cytokine Release Syndrome (CRS): IMDELLTRA® can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in 55% of patients who received IMDELLTRA®, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRA® was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA® was 14.6 hours (range: 2 to 566 hours).Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).Administer IMDELLTRA® following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA® infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRA® in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA®.Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA®. At the first sign of CRS, immediately discontinue IMDELLTRA® infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA® based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur. Neurologic Toxicity, Including ICANS: IMDELLTRA® can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in 47% of patients who received IMDELLTRA®, including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).ICANS occurred in 9% of IMDELLTRA®-treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRATM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRATM. The median time to resolution of ICANS was 33 days (range: 1 to 93 days).The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and receiving IMDELLTRA® are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRA® or permanently discontinue based on severity. Cytopenias: IMDELLTRA® can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRA®-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRA®.Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA®. Infections: IMDELLTRA® can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in 41% of patients who received IMDELLTRA®. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%).Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRA® and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA® based on severity. Hepatotoxicity: IMDELLTRA® can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA®, before each dose, and as clinically indicated. Withhold IMDELLTRA® or permanently discontinue based on severity. Hypersensitivity: IMDELLTRA® can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRA® and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA® based on severity. Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA® may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA® and for 2 months after the last dose. ADVERSE REACTIONS The most common (> 20%) adverse reactions were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%) and nausea (22%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%). Serious adverse reactions occurred in 58% of patients. Serious adverse reactions in > 3% of patients included CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%). Fatal adverse reactions occurred in 2.7% of patients including pneumonia (0.5%), aspiration (0.5%), pulmonary embolism (0.5%), respiratory acidosis (0.5%), and respiratory failure (0.5%). DOSAGE AND ADMINISTRATION: Important Dosing Information Administer IMDELLTRA® as an intravenous infusion over one hour. Administer IMDELLTRA® according to the step-up dosing schedule in the IMDELLTRA® PI (Table 1) to reduce the incidence and severity of CRS. For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRA® infusions to reduce the risk of CRS reactions as described in the PI (Table 3). IMDELLTRA® should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS. Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA® infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting. Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA® following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver. Prior to administration of IMDELLTRA® evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated. Ensure patients are well hydrated prior to administration of IMDELLTRA®. Please see IMDELLTRA® full Prescribing Information, including BOXED WARNINGS. Amgen Forward-Looking StatementsThis news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast), our acquisitions of ChemoCentryx, Inc. or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions, including those resulting from geopolitical relations and government actions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our sustainability objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. Any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media)Justin Claeys, 805-313-9775 (investors) REFERENCES: DeLLphi-304 Clinical Trial Listing. Available at: Accessed March 24, 2025. Paz-Ares, et al. JCO. 41, TPS8611-TPS8611(2023). DOI:10.1200/JCO.2023.41.16_suppl.TPS8611 Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer. Clin Cancer Res. 2021;27:1526-1537. Baeuerle PA, Kufer P, Bargou R. BiTE: Teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther. 2009;11:22-30. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389:2063-2075. Rojo F, Corassa M, Mavroudis D, et al. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer. 2020;147:237-243. PDQ® Adult Treatment Editorial Board. PDQ Small Cell Lung Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated June 27, 2024. Available at: Accessed March 25, 2025. World Health Organization. Lung. 2022. Available at: Accessed on March 24, 2025. Oronsky B, Abrouk N, Caroen S, et al. A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC). J Cancer. 2022;13:2945-2953. Sabari JK, Lok BH, Laird JH, et al. Unravelling the biology of SCLC: implications for therapy. Nat Rev Clin Oncol. 2017;14:549-561. Clinical Trials. Tarlatamab Clinical Trial Listings. Accessed March 25, 2025. 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Newsweek
2 days ago
- Health
- Newsweek
Research Shows This Action Can Increase Colon Cancer Survival Rate
Based on facts, either observed and verified firsthand by the reporter, or reported and verified from knowledgeable sources. Newsweek AI is in beta. Translations may contain inaccuracies—please refer to the original content. A new study published by The New England Journal of Medicine on Sunday shows that adding an exercise program to recovery plans following treatment for colon cancer increased survival rates. Newsweek has reached out to the leaders of the study via email for information during non-working hours Sunday. Why It Matters Across the globe, colorectal cancer rates have skyrocketed, especially among millennials, with a 2024 study published by The Lancet showing those born in 1990 being two to three times more likely to have issues than those born in 1955. Colorectal cancer is the second most deadly and the third most prevalent in the world. In the United States, colorectal cancer is the fourth most common cancer for men and women, according to the Colorectal Cancer Alliance (CCA). Symptoms of colorectal cancers can include a change in bathroom habits, cramps, weight loss as well as blood in the stool, which can still look normal, according to These cancers can cause bleeding in the digestive tract and lead to anemia. Those who experience these symptoms should get tested by a medical professional. "Sometimes the first sign of colorectal cancer is a blood test showing a low red blood cell count," the American Cancer Society's website says. A stock photo shows people exercising at a gym. A stock photo shows people exercising at a gym. Getty What To Know The study followed patients in 55 medical centers for a three-year period following their initial treatment of surgery and chemotherapy. Over a 15-year period from 2009 to 2024, more than 800 patients were designated into either a health education group or exercise group. Researchers found that patients who began a three-year exercise program following chemotherapy had "significantly longer disease-free survival and findings consistent with longer overall survival." The study broke people up into two groups, a health-education program or a health education program in addition to a monitored exercise regime as part of the Colon Health and Lifelong Exercise Change. Both were done through the Canadian Cancer Trials Group. Of those who were a part of the exercise program, 80.3 percent saw a five-year disease-free survival, while 73.9 percent of the health-education group saw the same results. "Preclinical and observational studies suggest that exercise may improve cancer outcomes," the study said, adding that "definitive evidence" was lacking, hence the launch of this study. The exercise program participants received behavioral-support sessions as well as 12 in-person exercise sessions over two weeks for the first six months of the study. In the following six months, as part of phase two, patients continued to go to the support sessions either in person or virtually, along with their supervised exercise sessions. The last two years of the study required patients to go to in-person or remote support sessions, along with supervised exercise sessions, for those attending the support sessions in person. "Results support longer overall survival in the exercise group than in the health-education group," the study says. The study said that people who suffer from these diseases often have less quality of life and physical function issues, which the exercise program aims to help. "Interventions that improve both survival and quality of life in this patient population are needed," according to the study. However, even after treatment, recurrence happens 20 to 40 percent of patients, but the exercise program can cut that risk down, the new study shows. What People Are Saying Dr. Christopher Booth, a co-chair of the international study and a medical oncologist at Kingston Health Sciences Centre in Kingston, Ontario, told The Candian Press: "It's the first clinical trial in the world asking whether exercise can improve cancer survival. And in fact, the results were we had a cancer drug with this amount of benefit, it would cost between $100,000 and $200,000 per year (and) it would be celebrated in all the major guidelines across oncology societies worldwide." What Happens Next? Even after treatment, recurrence happens 20 to 40 percent of patients, but an exercise program can cut the risk down, according to the new study. Those who have received treatment for colorectal cancer should talk to their doctor before starting any exercise programs.
Business Wire
4 days ago
- Business
- Business Wire
ENHERTU ® Reduced the Risk of Death by 30% Versus Ramucirumab Plus Paclitaxel as a Second-Line Therapy in Patients with HER2 Positive Unresectable or Metastatic Gastric Cancer in DESTINY-Gastric04 Phase 3 Trial
TOKYO & BASKING RIDGE, N.J.--(BUSINESS WIRE)--Positive results from the DESTINY-Gastric04 phase 3 trial showed ENHERTU ® (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared to ramucirumab plus paclitaxel in patients with second-line HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Results will be presented today as a late-breaking oral presentation (LBA #4002) at the 2025 American Society of Clinical Oncology (#ASCO25) Annual Meeting and simultaneously published in The New England Journal of Medicine. ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). In the primary endpoint analysis of OS, ENHERTU reduced the risk of death by 30% versus ramucirumab plus paclitaxel (hazard ratio [HR]: 0.70; confidence interval [CI]: 0.55-0.90; p=0.0044). Median OS was 14.7 months with ENHERTU (n=246) versus 11.4 months with ramucirumab plus paclitaxel (n=248). In the secondary endpoint analysis of progression-free survival (PFS), ENHERTU demonstrated a 26% reduction in the risk of disease progression or death versus ramucirumab plus paclitaxel (HR: 0.74; 95% CI: 0.59-0.92; p=0.0074) as assessed by investigator. Median PFS was 6.7 months with ENHERTU versus 5.6 months with ramucirumab plus paclitaxel. A confirmed objective response rate (ORR) of 44.3% (95% CI: 37.8-50.9) was seen in patients treated with ENHERTU with seven complete responses (CR) and 97 partial responses (PR) versus an ORR of 29.1% (95% CI: 23.4-35.3) with three CRs and 66 PRs in the ramucirumab plus paclitaxel arm (p=0.0006). Median duration of response (DOR) was 7.4 months (95% CI: 5.7-10.1) in the ENHERTU arm and 5.3 months (95% CI: 4.1-5.7) in the ramucirumab plus paclitaxel arm. Disease control rate (DCR) was 91.9% (95% CI: 87.7-95.1) with ENHERTU versus 75.9% (95% CI: 70.0-81.2) with ramucirumab plus paclitaxel. Improvements in OS and PFS with ENHERTU were consistent across subgroups. 'Gastric cancer is particularly challenging to treat, especially in the advanced stages where the five-year survival rate remains low,' said Kohei Shitara, MD, Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan and lead investigator in the DESTINY-Gastric04 trial. 'The superior overall survival demonstrated in DESTINY-Gastric04 confirms that ENHERTU could become the global standard of care in the second-line metastatic setting of HER2 positive gastric cancer or gastroesophageal junction cancer.' The safety profile of ENHERTU in DESTINY-Gastric04 was consistent with previous gastric cancer clinical trials with no new safety concerns identified. The most common grade 3 or higher treatment related adverse events occurring in patients treated with ENHERTU were neutropenia (28.7%), anemia (13.9%), thrombocytopenia (8.6%), leukopenia (7.4%) and fatigue (7.0%). Interstitial lung disease (ILD) or pneumonitis occurred in 13.9% of patients treated with ENHERTU and 1.3% treated in the ramucirumab plus paclitaxel arm. In the ENHERTU arm, the majority of ILD or pneumonitis events were low grade (grade 1 [n=7; 2.9%] or grade 2 [n=26; 10.7%]) except for one grade 3 ILD event (0.4%) as determined by an independent adjudication committee. In the ramucirumab plus paclitaxel arm, there were two grade 3 (0.9%) and one grade 5 (0.4%) ILD events. 'ENHERTU continues to deliver impressive results with these new data from DESTINY-Gastric04, which represent the first time a HER2 directed medicine has demonstrated a survival benefit in a randomized phase 3 trial in the second-line HER2 positive metastatic gastric cancer setting,' said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. 'Similar to our strategy in other tumor types, we continue to pursue the development of ENHERTU in earlier stages of gastric cancer and have recently initiated phase 3 trials evaluating ENHERTU as part of a combination regimen as a first-line treatment in patients HER2 positive metastatic disease.' 'Patients with HER2 positive metastatic gastric cancer who experience progression after first-line treatment have historically faced poor outcomes,' said Cristian Massacesi, MD, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca. 'These results showed that ENHERTU reduced the risk of death by nearly one-third in patients with previously treated HER2 positive metastatic gastric cancer, reinforcing the benefit of ENHERTU in this setting.' ENHERTU is currently approved in more than 70 countries in the second-line or third-line metastatic setting of HER2 positive gastric cancer based on DESTINY-Gastric01, a randomized phase 2 trial, and DESTINY-Gastric02 and DESTINY-Gastric06, two single-arm phase 2 trials. Daiichi Sankyo and AstraZeneca are currently evaluating ENHERTU in the first-line metastatic setting through the DESTINY-Gastric05 and ARETEMIDE-Gastric01 phase 3 trials. The majority of patients in the DESTINY-Gastric04 trial had received no prior treatment with an immune checkpoint inhibitor (84.1% in the ENHERTU arm and 84.7% in the ramucirumab plus paclitaxel arm) and had two or more metastatic sites (70.3% in the ENHERTU arm and 69.8% in the ramucirumab plus paclitaxel arm). Median duration of follow-up was 16.8 months in the ENHERTU arm and 14.4 months in the ramucirumab plus paclitaxel arm. Median treatment duration was 5.4 months (range: 0.7-30.3) with ENHERTU and 4.6 months (range: 0.9-34.9) with ramucirumab plus paclitaxel. Of the patients that discontinued treatment from the ramucirumab plus paclitaxel arm, 52 (21.0%) proceeded to receive ENHERTU and 12 (4.8%) disitamab vedotin post-trial. As of the data cut-off of October 24, 2024, 18.9% of patients receiving ENHERTU and 18.5% receiving ramucirumab plus paclitaxel remained on study treatment. Efficacy Measure ENHERTU (6.4 mg/kg) n = 246 Ramucirumab plus Paclitaxel i n = 248 Median OS, months (95% CI) 14.7 months 11.4 months HR = 0.70 (0.55-0.90) p = 0.0044 Median PFS, months (95% CI) 6.7 months 5.6 months HR = 0.74 (0.59-0.92) p = 0.0074 Confirmed ORR i,ii, % (95% CI) 44.3% (37.8-50.9) 29.1% (23.4-35.3) p = 0.0006 CR, % (n) 3.0% (7) 1.3% (3) PR, % (n) 41.3% (97) 27.8% (66) SD, % (n) 47.7% (112) 46.8% (111) PD, % (n) 5.5% (13) 9.3% (22) NE, % (n) 2.6% (6) 14.8% (35) DOR iii,iv, months (95% CI) 7.4 months (5.7-10.1) 5.3 months (4.1-5.7) DCR v, % (95% CI) 91.9 (87.7-95.1) 75.9 (70.0-81.2) CI, confidence interval; DCR, disease control rate; NE, not evaluable; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; SD, stable disease i ORR is CR + PR ii Confirmed ORR represents responses confirmed by a follow-up scan ≥four weeks after initial CR/PR iii Based on investigator assessment iv Based on ORR eligible patients; ORR eligible patients are those who were randomly assigned at least 77 days (i.e., 2 × 6 weeks - 1 week) before DCO date of interim analyses v DCR is CR + PR + SD Expand About DESTINY-Gastric04 DESTINY-Gastric04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/kg) versus ramucirumab and paclitaxel in patients with HER2 positive (IHC 3+ or IHC 2+/ISH+) unresectable and/or metastatic gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen. The primary endpoint is OS. Secondary endpoints include investigator-assessed progression-free survival, objective response rate, duration of response, disease control rate and safety. In March 2025, an Independent Data Monitoring Committee recommended unblinding DESTINY-Gastric04 based on the superior efficacy of ENHERTU seen at a planned interim analysis. DESTINY-Gastric04 enrolled 494 patients in Asia, Europe and South America. For more information about the trial, visit About HER2 Positive Gastric Cancer Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death. 1 Approximately one million cases of gastric cancer were diagnosed in 2022. 1 Gastric cancer is associated with a poor prognosis, particularly in advanced stages of the disease where the five-year survival rate is 5% to 10%. 2 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including gastric cancer. 3 Approximately one in five gastric cancers are considered HER2 positive. 3,4 Prior to the results of the DESTINY-Gastric04 trial of ENHERTU, no other HER2 directed medicine has demonstrated a survival benefit in the second-line metastatic setting in a randomized clinical trial. 5 About ENHERTU ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo's proprietary DXd ADC Technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca's ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 positive (immunohistochemistry [IHC] 3+ or in-situ hybridization (ISH)+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. ENHERTU (5.4 mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR) positive, HER2 low (IHC 1+ or IHC 2+/ISH-) or HER2 ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that has progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 60 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/kg) is approved in more than 70 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia, Saudi Arabia, Taiwan, U.K. and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY ® in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo's DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. ENHERTU U.S. Important Safety Information Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: In the metastatic setting, or In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy Unresectable or metastatic: Hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen Unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Contraindications None. Warnings and Precautions Interstitial Lung Disease / Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21). Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 10 9 /L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 10 9 /L and temperature >38.3° C or a sustained temperature of ≥38° C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1.2% of patients. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients. Left Ventricular Dysfunction Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is 20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of 20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment. HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF. Embryo-Fetal Toxicity ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU. Additional Dose Modifications Thrombocytopenia For Grade 3 thrombocytopenia (platelets <50 to 25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 10 9 /L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level. Adverse Reactions HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINYBreast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%). HER2-Positive Metastatic Breast Cancer DESTINY-Breast03 The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU. Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each). ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%). HER2-Low and HER2-Ultralow Metastatic Breast Cancer DESTINY-Breast06 The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU. Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each). ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%). DESTINY-Breast04 The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU. Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each). ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%). HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg) DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis. The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY-Lung02. Nineteen percent of patients were exposed for >6 months. Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%). ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients. The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%). HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m 2 biweekly or paclitaxel (N=7) 80 mg/m 2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU. Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%). ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%). HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2). Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock. ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea. The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%). Use in Specific Populations Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU. Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose. Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility: ENHERTU may impair male reproductive function and fertility. Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients. Geriatric Use: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg, 24% were ≥65 years and 4.9% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (61%) as compared to younger patients (52%). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were ≥65 years and 9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min). Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST). To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide. About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit
Yahoo
4 days ago
- Business
- Yahoo
Advanced colon cancer patients lived twice as long with a Pfizer combo therapy, trial finds
A combination drug treatment doubled survival time for patients with an aggressive form of colorectal cancer, according to late-stage trial data published Friday in The New England Journal of Medicine and presented at the American Society of Clinical Oncology's annual meeting in Chicago. The three-treatment combination included a standard chemotherapy drug, an antibody drug called cetuximab and a pill from Pfizer called Braftovi, which targets a cancer mutation called BRAF V600E. The mutation shows up in about 10% of patients with colorectal cancer, said Dr. Lionel Kankeu Fonkoua, a gastrointestinal oncologist at the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota. Patients with the mutation tend to survive for less than a year after diagnosis, and they often don't respond well to standard chemotherapy treatments, said Fonkoua, who wasn't involved with the new trial. According to Pfizer, the risk of death for these patients is more than double compared with those without the mutation. Braftovi was initially approved in 2020 to be used with cetuximab in this group of patients after other treatments had failed. The new trial looked at the drug combination as a so-called first-line therapy. The Food and Drug Administration granted the treatment fast-track approval as a first-line approach in December on the condition that Pfizer provide additional data confirming its effectiveness. The agency often grants fast-track approval to treatments that address serious or life-threatening conditions, especially when there's an unmet medical need. Dr. Christopher Lieu, a professor of medicine at the University of Colorado School of Medicine who wasn't involved with the research, called the results 'very impactful.' 'Patients are clearly living longer, and this represents the new standard of care for this specific subset of patients with this specific mutation,' Lieu said. The trial included more than 600 patients with the mutation who had metastatic colorectal cancer. Patients were randomized to get either the three-drug combination treatment or standard chemotherapy alone. Some of the patients in the latter group were also given bevacizumab, a first-line treatment for metastatic colorectal cancer. The trial found that patients who got the combination treatment lived, on average, about 30 months, compared with about 15 months for those who got standard chemotherapy, with or without bevacizumab. What's more, 47% of patients who got the combination treatment had no disease progression after two years, meaning their cancer didn't grow or spread. The treatment was well-tolerated, with no unexpected safety concerns that would've caused investigators to stop the trial. 'This is a really remarkable finding,' said Dr. Scott Kopetz, a professor of gastrointestinal medical oncology at the MD Anderson Cancer Center in Texas and a co-principal investigator in the trial. 'When we bring this together with standard of care chemotherapy, we get really substantially prolonged survival for these patients that are really unprecedented for this disease type.' More than 141,000 new cases of colorectal cancer are diagnosed in the U.S. each year, making it the fourth most common cancer, according to the Centers for Disease Control and Prevention. About 52,900 people in the U.S. are expected to die from colorectal cancer this year, according to the American Cancer Society. Laurie Ritchie, 61, of St. Louis, got the combination treatment in October 2023. Her results weren't included in the clinical trial analysis. Ritchie had been diagnosed with metastatic colorectal cancer with the BRAF mutation — a diagnosis she describes as 'a huge shock.' Previous colonoscopies hadn't detected cancer; by the time she was diagnosed, the cancer had already reached Stage 4. It eventually spread to her lungs and ovaries. Since she got the combination treatment, she said her blood tests have consistently shown no trace of cancer. While she still worries about the cancer coming back, she says she's now focused on living fully — including going water skiing and downhill skiing. 'I've kind of learned to think of it as something in the trunk, not in the front seat,' she said. 'It still feels a bit like a ticking time bomb inside me, but I think the work I've done on my mental health has really helped me live with it.' This article was originally published on
NBC News
5 days ago
- Health
- NBC News
Advanced colon cancer patients lived twice as long with a Pfizer combo therapy, trial finds
A combination drug treatment doubled survival time for patients with an aggressive form of colorectal cancer, according to late-stage trial data published Friday in The New England Journal of Medicine and presented at the American Society of Clinical Oncology's annual meeting in Chicago. The three-treatment combination included a standard chemotherapy drug, an antibody drug called cetuximab and a pill from Pfizer called Braftovi, which targets a cancer mutation called BRAF V600E. The mutation shows up in about 10% of patients with colorectal cancer, said Dr. Lionel Kankeu Fonkoua, a gastrointestinal oncologist at the Mayo Clinic Comprehensive Cancer Center in Rochester, Minnesota. Patients with the mutation tend to survive for less than a year after diagnosis, and they often don't respond well to standard chemotherapy treatments, said Fonkoua, who wasn't involved with the new trial. According to Pfizer, the risk of death for these patients is more than double compared with those without the mutation. Braftovi was initially approved in 2020 to be used with cetuximab in this group of patients after other treatments had failed. The new trial looked at the drug combination as a so-called first-line therapy. The Food and Drug Administration granted the treatment fast-track approval as a first-line approach in December on the condition that Pfizer provide additional data confirming its effectiveness. The agency often grants fast-track approval to treatments that address serious or life-threatening conditions, especially when there's an unmet medical need. Dr. Christopher Lieu, a professor of medicine at the University of Colorado School of Medicine who wasn't involved with the research, called the results 'very impactful.' 'Patients are clearly living longer, and this represents the new standard of care for this specific subset of patients with this specific mutation,' Lieu said. The trial included more than 600 patients with the mutation who had metastatic colorectal cancer. Patients were randomized to get either the three-drug combination treatment or standard chemotherapy alone. Some of the patients in the latter group were also given bevacizumab, a first-line treatment for metastatic colorectal cancer. The trial found that patients who got the combination treatment lived, on average, about 30 months, compared with about 15 months for those who got standard chemotherapy, with or without bevacizumab. What's more, 47% of patients who got the combination treatment had no disease progression after two years, meaning their cancer didn't grow or spread. The treatment was well-tolerated, with no unexpected safety concerns that would've caused investigators to stop the trial. 'This is a really remarkable finding,' said Dr. Scott Kopetz, a professor of gastrointestinal medical oncology at the MD Anderson Cancer Center in Texas and a co-principal investigator in the trial. 'When we bring this together with standard of care chemotherapy, we get really substantially prolonged survival for these patients that are really unprecedented for this disease type.' More than 141,000 new cases of colorectal cancer are diagnosed in the U.S. each year, making it the fourth most common cancer, according to the Centers for Disease Control and Prevention. About 52,900 people in the U.S. are expected to die from colorectal cancer this year, according to the American Cancer Society. Laurie Ritchie, 61, of St. Louis, got the combination treatment in October 2023. Her results weren't included in the clinical trial analysis. Ritchie had been diagnosed with metastatic colorectal cancer with the BRAF mutation — a diagnosis she describes as 'a huge shock.' Previous colonoscopies hadn't detected cancer; by the time she was diagnosed, the cancer had already reached Stage 4. It eventually spread to her lungs and ovaries. Since she got the combination treatment, she said her blood tests have consistently shown no trace of cancer. While she still worries about the cancer coming back, she says she's now focused on living fully — including going water skiing and downhill skiing. 'I've kind of learned to think of it as something in the trunk, not in the front seat,' she said. 'It still feels a bit like a ticking time bomb inside me, but I think the work I've done on my mental health has really helped me live with it.'
