Latest news with #BREAKWATER
Medscape
a day ago
- Business
- Medscape
Targeted Therapy Wins Big for BRAF-Mutated Metastatic CRC
The latest results from the BREAKWATER trial have confirmed encorafenib plus cetuximab with chemotherapy as the new first-line standard of care for BRAF V600E-mutant metastatic colorectal cancer (CRC), according to research presented at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. At the interim analysis, encorafenib plus cetuximab with mFOLFOX6 chemotherapy doubled median overall survival compared with the current standard of care — investigators' choice of chemotherapy with or without bevacizumab. In addition, at a median follow-up of 16.8 months, the new treatment regimen led to a significant improvement in median progression-free survival of almost 6 months. This survival finding is 'unprecedented' and 'practice changing' for these patients who historically have a poor prognosis, said lead investigator and presenter Elena Élez, MD, PhD, a gastrointestinal medical oncologist at the Vall d'Hebron University Hospital in Barcelona, Italy. The study was published in The New England Journal of Medicine to coincide with Élez's presentation. BRAF mutations, which occur in up to 12% of patients with metastatic CRC, are associated with poor outcomes. In December 2024, the US Food and Drug Administration (FDA) granted accelerated approval for the BRAF inhibitor encorafenib alongside cetuximab and mFOLFOX6 for patients with metastatic CRC and a BRAF V600E mutation. This approval was based on earlier results from BREAKWATER that showed a 21% higher objective response rate and a longer duration of response with this regimen. The accelerated approval means that this regimen has already been making its way into the clinic, but 'we were all waiting for this [latest] data,' Pamela Kunz, MD, chief of Gastrointestinal Medical Oncology at Yale University in New Haven, Connecticut, told Medscape Medical News . The doubling of overall survival 'is a big deal,' she said. In the trial, patients were randomly assigned to receive either first-line encorafenib plus cetuximab with mFOLFOX6 (n = 236) or to a control group — physician's choice of either mFOLFOX6, FOLFOXIRI, or CAPOX chemotherapy (n = 243). Most patients in the control arm also received the tumor angiogenesis inhibitor bevacizumab. The broad options in the control arm speak to how heterogeneous treatment has been for BRAF V600E-mutant metastatic CRC, said study discussant Andrea Sartore-Bianchi, MD, a medical oncologist at the University of Milan, Milan, Italy. Patients in the trial had received no prior systemic therapy for metastatic disease. Investigators excluded patients with high levels of microsatellite instability because they are candidates for immunotherapy. At a median follow-up of 16.8 months, median progression-free survival was 12.8 months for the encorafenib group compared with 7.1 months for the control group (hazard ratio [HR], 0.53; P < .0001). At a median follow-up of 22 months, overall survival was 30 months in the encorafenib group compared with 15 months in the control group (HR, 0.49; P < .0001). The benefits of the combination were held up in high-risk subgroups, including in patients with liver metastases and those with metastases in three or more organs. With the use of more agents and a longer duration of treatment due to improved efficacy, there was an expected increase in toxicity with the new regimen. The rate of treatment-related grade 3/4 adverse events was 76.3% with encorafenib vs 58.5% with the control regimen. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation. BREAKWATER also included an encorafenib plus cetuximab arm without chemotherapy, but enrollment was stopped early at 158 patients due to possible futility. Still, these patients had as good or numerically better outcomes than the control group, which means the drug combination alone is a valid option for those unable to tolerate chemotherapy, said Élez. 'The results are striking,' said Sartore-Bianchi in his discussion. 'Now that we have the big picture' from BREAKWATER, the combination should be considered the first-line standard of care. Mark A. Lewis, MD, a gastrointestinal medical oncologist at Intermountain Healthcare in Murray, Utah, explained that what usually happens in metastatic CRC is that people are treated with chemotherapy for a bit before oncologists notice the tumor is behaving more aggressively than expected and order a BRAF test. This delay is now 'completely unacceptable,' he told Medscape Medical News . The takeaway from BREAKWATER is that testing must come sooner. To help with BRAF testing, the FDA approved the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit. 'As soon as you know patients are BRAF -mutated, you need to play your entire hand' because it will double survival,' said Lewis. 'This absolutely validates a biomarker-informed approach to colon cancer,' similar to what we have in breast cancer. BREAKWATER was funded primarily by Pfizer, maker of encorafenib, with support from Eli Lilly and Merck, who jointly market cetuximab. Élez reported numerous ties to the companies, including research grants, travel funding, honoraria, and/or consultant work. Lewis, Kunz, and Sartore-Bianchi had no relationships with the firms.
Yahoo
7 days ago
- Business
- Yahoo
ASCO25: Pfizer's Braftovi combo boasts 47% drop in disease progression in mCRC
Pfizer's Braftovi (encorafenib) combination therapy was shown to reduce the risk of death by nearly half compared to standard of care (SOC) for metastatic colorectal cancer (mCRC) patients with BRAF V600E mutation. The company announced the survival benefit in an abstract at the American Society of Clinical Oncology (ASCO) 2025 conference being held in Chicago, Illinois, between 30 May and 3 June. The results will be presented on the first day of the conference by Dr Elena Élez, co-principal investigator of the BREAKWATER trial, including primary progression-free survival (PFS) data and updated analysis of overall survival (OS). The presentation includes new data from Pfizer's Phase III trial (NCT04607421) of Braftovi in combination with Eli Lilly's Erbitix (cetuximab) and mFOLFOX6 chemotherapy (fluorouracil, leucovorin, and oxaliplatin) in mCRC patients with BRAF V600E mutation. In the study, the regimen elicited a 47% decreased risk of disease progression, with median PFS for treated patients at 12.8 months versus 7.1 months with SOC. An updated analysis of the trial's key secondary endpoint also shows the regimen led to a median OS of 30.3 months compared to 15.1 months with SOC, equating to a 51% reduction in risk of death for patients. As per a 30 May press release, Élez said: 'The BREAKWATER results are the first promising survival outcomes ever reported for BRAF-mutant mCRC in the first-line setting.' The combination was previously approved by the US Food and Drug Administration (FDA) for adult mCRC patients with CRAF V600E mutation following prior therapy in April 2020. The regimen has since gained accelerated approval as a first-line treatment in December 2024, based on interim overall response rate (ORR) data from the BREAKWATER study, with the full approval contingent on continued demonstration of efficacy. Braftovi is a small-molecule inhibitor of BRAF, a protein involved in tumour cell growth, while Erbitux is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR). GlobalData projects the drugs to generate total annual sales of $1.14bn and $1.98bn by 2031, respectively. GlobalData is the parent company of Clinical Trials Arena. Pfizer's hopes to entrench Braftovi as part of the SOC for mCRC were expressed by the company's chief oncology development officer, Dr Joanna Bendell. Colorectal cancer is the third most common type of cancer globally, and BRAF V600E mutations occur in between 8% and 12% of patients. Presently, this subpopulation of patients exhibits a risk of mortality double that of patients with no known BRAF mutation. "ASCO25: Pfizer's Braftovi combo boasts 47% drop in disease progression in mCRC" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Error while retrieving data Sign in to access your portfolio Error while retrieving data Error while retrieving data Error while retrieving data Error while retrieving data
Yahoo
7 days ago
- Business
- Yahoo
ASCO25: Pfizer's Braftovi combo boasts 47% drop in disease progression in mCRC
Pfizer's Braftovi (encorafenib) combination therapy was shown to reduce the risk of death by nearly half compared to standard of care (SOC) for metastatic colorectal cancer (mCRC) patients with BRAF V600E mutation. The company announced the survival benefit in an abstract at the American Society of Clinical Oncology (ASCO) 2025 conference being held in Chicago, Illinois, between 30 May and 3 June. The results will be presented on the first day of the conference by Dr Elena Élez, co-principal investigator of the BREAKWATER trial, including primary progression-free survival (PFS) data and updated analysis of overall survival (OS). The presentation includes new data from Pfizer's Phase III trial (NCT04607421) of Braftovi in combination with Eli Lilly's Erbitix (cetuximab) and mFOLFOX6 chemotherapy (fluorouracil, leucovorin, and oxaliplatin) in mCRC patients with BRAF V600E mutation. In the study, the regimen elicited a 47% decreased risk of disease progression, with median PFS for treated patients at 12.8 months versus 7.1 months with SOC. An updated analysis of the trial's key secondary endpoint also shows the regimen led to a median OS of 30.3 months compared to 15.1 months with SOC, equating to a 51% reduction in risk of death for patients. As per a 30 May press release, Élez said: 'The BREAKWATER results are the first promising survival outcomes ever reported for BRAF-mutant mCRC in the first-line setting.' The combination was previously approved by the US Food and Drug Administration (FDA) for adult mCRC patients with CRAF V600E mutation following prior therapy in April 2020. The regimen has since gained accelerated approval as a first-line treatment in December 2024, based on interim overall response rate (ORR) data from the BREAKWATER study, with the full approval contingent on continued demonstration of efficacy. Braftovi is a small-molecule inhibitor of BRAF, a protein involved in tumour cell growth, while Erbitux is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR). GlobalData projects the drugs to generate total annual sales of $1.14bn and $1.98bn by 2031, respectively. GlobalData is the parent company of Clinical Trials Arena. Pfizer's hopes to entrench Braftovi as part of the SOC for mCRC were expressed by the company's chief oncology development officer, Dr Joanna Bendell. Colorectal cancer is the third most common type of cancer globally, and BRAF V600E mutations occur in between 8% and 12% of patients. Presently, this subpopulation of patients exhibits a risk of mortality double that of patients with no known BRAF mutation. "ASCO25: Pfizer's Braftovi combo boasts 47% drop in disease progression in mCRC" was originally created and published by Pharmaceutical Technology, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Yahoo
27-01-2025
- Business
- Yahoo
Pfizer reports positive outcomes from trial of mCRC combination therapy
Pfizer has reported positive outcomes from the Phase III BREAKWATER trial of BRAFTOVI plus cetuximab and mFOLFOX6 for treating metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. The study evaluated the combination against standard chemotherapy, with or without bevacizumab. During the period of analysis, the combination showed a clinically meaningful and statistically significant improvement in confirmed objective response rate as per blinded independent central review. Subjects treated with the combination regimen had a median time to respond of 7.1 weeks, with 22.4% experiencing a response lasting a minimum of one year. In contrast, only 11.4% of subjects on standard chemotherapy achieved a similar duration of response. Although overall survival (OS) data was not mature, there was a 'promising' trend favouring the combo regimen. The trial is underway for OS and progression-free survival (PFS). Outcomes of PFS are anticipated this year. The BREAKWATER trial's safety profile for the combination was consistent with expectations, showing no new safety signals. Serious treatment-emergent adverse events were slightly higher in the BRAFTOVI group than in the control group. Pfizer chief oncology officer Roger Dansey said: 'These results of this first analysis were the basis for the first approval of a targeted therapy regimen for use in the first-line setting for patients with metastatic colorectal cancer with a BRAF V600E mutation. 'We are highly encouraged by these response results, which are indicative of the clinically meaningful benefit of BRAFTOVI in reducing tumour size or having no detectable cancer, along with the promising interim analysis of overall survival.' The US Food and Drug Administration granted accelerated approval to the combination regimen last month, under Project FrontRunner. Discussions with other regulatory authorities are ongoing to support potential future licence applications for the regimen. Earlier this month, the company's CREST trial assessing sasanlimab with Bacillus Calmette-Guérin (BCG), as induction treatment with or without maintenance in individuals with BCG-naive, high-risk non-muscle invasive bladder cancer, met its primary endpoint. "Pfizer reports positive outcomes from trial of mCRC combination therapy" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site.
