Latest news with #randomized
Medscape
31-07-2025
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- Medscape
Novel Combo Boosts Survival in IDH1-Mutated AML
TOPLINE: Ivosidenib combined with azacitidine extended median overall survival to 29.3 months compared with 7.9 months for placebo plus azacitidine in newly diagnosed isocitrate dehydrogenase 1 (IDH1)-mutated acute myeloid leukemia (AML). The combination therapy also improved hematologic recovery and increased transfusion independence rate to 53.8% vs 17.1% with placebo. METHODOLOGY: A total of 148 patients with newly diagnosed IDH1-mutated AML who were unfit for intensive chemotherapy were randomized to receive either ivosidenib-azacitidine (n = 73) or placebo-azacitidine (n = 75). Treatment consisted of 500 mg ivosidenib or placebo administered orally once daily, combined with subcutaneous or intravenous 75 mg/m² azacitidine for 7 days in 28-day cycles, with randomization stratified by geographic region and disease status. Analysis included a median follow-up period of 28.6 months, with overall survival as the key outcome measure, along with hematologic recovery, transfusion independence, and molecular measurable residual disease response. TAKEAWAY: Median overall survival was significantly longer with ivosidenib-azacitidine at 29.3 months (95% CI, 13.2-not reached) compared to 7.9 months (95% CI, 4.1-11.3) with placebo-azacitidine (hazard ratio [HR], 0.42; 95% CI, 0.27-0.65; P < .0001). Among patients who were transfusion dependent at baseline, conversion to transfusion independence was achieved in 53.8% (21/39) of ivosidenib-azacitidine patients vs 17.1% (7/41) of placebo-azacitidine patients (P = .0004). Of 33 ivosidenib-treated patients evaluable for molecular measurable residual disease, 10 (30.3%) achieved MRD negativity by day 1 of cycle 14, all of whom had complete remission. The safety profile remained consistent with previous reports, with lower rates of febrile neutropenia and infections in the ivosidenib-azacitidine arm, though neutropenia and bleeding events were more common than with placebo. IN PRACTICE: 'These long-term efficacy and safety results confirm the benefit of ivosidenib-azacitidine in this challenging-to-treat population and support its use as a standard of care with the longest reported survival benefit for intensive chemotherapy-ineligible patients with IDH1-mutated AML,' the authors of the study wrote. SOURCE: The study was led by Pau Montesinos, Hospital Universitari i Politécnic La Fe in Valencia, Spain, and Hartmut Döhner, Ulm University Hospital in Ulm, Germany. It was published online in Blood Advances. LIMITATIONS: According to the authors, molecular response analysis was limited by the small number of measurable residual disease-evaluable patients and samples, as well as the discontinuation of sample collection after study unblinding in March 2021. The limited number of variants that could be tracked with sufficient sensitivity in panel-based next-generation sequencing measurable residual disease assessment also constrained the molecular analyses. DISCLOSURES: Montesinos disclosed having relationships with AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, Sanofi, Servier, and Teva Pharmaceuticals. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
28-07-2025
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- Medscape
Secukinumab in Early PsA Starts Fast vs Standard of Care
TOPLINE: More patients with recently diagnosed psoriatic arthritis (PsA) saw clinical improvement by 3 months in a treat-to-target strategy with secukinumab, a monoclonal antibody targeting interleukin-17, compared with those on standard-of-care treatment, but this difference was not seen at later 3-month intervals out to 1 year. METHODOLOGY: In a randomized, open-label, manufacturer-sponsored, multicenter trial, 120 patients (mean age, 49; 41% women) diagnosed with PsA within the prior 3 months were randomized to a treat-to-target approach of early treatment with secukinumab or standard of care in which treatment escalated according to predetermined steps if patients failed to respond. At the start, in the secukinumab arm, 60 patients received 300 mg monthly secukinumab, a single injection of 80 mg triamcinolone, and 15 mg/wk methotrexate plus 10 mg/wk folic acid. In the standard-of-care arm, 60 patients received 80 mg triamcinolone (single injection), methotrexate starting at 15 mg/wk and increasing to 25 mg/wk by 6 weeks, and 10 mg/wk folic acid. In the standard-of-care arm, treatment was escalated by adding sulfasalazine 1000 mg twice daily if needed, then switching if needed to a first or second TNF inhibitor with methotrexate. In the secukinumab arm, patients with poor response were escalated to a TNF inhibitor with 25 mg methotrexate per week, followed by a second TNF inhibitor plus methotrexate if needed. Outcomes were measured at 3, 6, 9, and 12 months, and the primary endpoint was the percentage of patients achieving 50% or greater improvement in American College of Rheumatology response criteria (ACR50) at 6 months. TAKEAWAY: At 6 months, both trial arms had similar ACR50 rates (around 41% in the secukinumab arm vs 37% in the standard-of-care arm). However, first-line secukinumab was associated with significantly more patients achieving ACR50 at 3 months (about 42% vs 22%; P < .05). Secondary endpoints of the percentage of patients meeting criteria for Minimal Disease Activity, 90% improvement in Psoriasis Area Severity Index, and resolution of enthesitis and dactylitis generally followed the same pattern of quicker responses in the secukinumab arm, followed by numerically greater but not statistically significant differences in the secukinumab vs standard-of-care arms at later timepoints. IN PRACTICE: 'Early response is very important to patients. They don't necessarily care whether they are eventually going to catch up. They want to know they'll feel much better at 3 months,' commented Dafna Gladman, MD, senior scientist at the Toronto Western Research Institute and professor in the Institute of Medical Science at the University of Toronto, both in Toronto, Ontario, Canada. She was not a part of the study. SOURCE: Gonul Hazal Koc, MD, of Erasmus MC in Rotterdam, the Netherlands, led the research and presented the 12-month results in a poster at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2025 Annual Meeting and Trainee Symposium in Bogotá, Colombia. LIMITATIONS: The study was not blinded, and a treat-to-target approach, while recommended by several guidelines, does not necessarily represent routine clinical practice in PsA. DISCLOSURES: Koc and her colleagues' research was supported by an unrestricted grant to her institution by Novartis, the manufacturer of secukinumab, which also supplied the study reported having no financial relationships outside the grant to her institution. Gladman has received research support and/or consultant fees from AbbVie, Amgen, Bristol-Myers Squibb, Johnson & Johnson, Eli Lilly, Fresenius Kabi, Novartis, Galapagos, UCB, Gilead, Janssen, Roche, and Pfizer.
Medscape
21-07-2025
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- Medscape
Tirzepatide Outperforms Semaglutide on Combined T2D Goals
'Simultaneous control of hyperglycemia, lipid profile, blood pressure, and body weight is essential for preventing chronic complications in type 2 diabetes,' Leite said. 'Yet only a small portion of individuals with T2D achieve the recommended therapeutic targets,' she noted. Numerous studies have shown that intensive interventions to meet all combined targets significantly reduce cardiovascular events and mortality, Leite noted. While GLP-1 medications show benefits in each of these measures, the superiority of tirzepatide, a dual GLP-1/ glucose-dependent insulinotropic polypeptide agonist has not been demonstrated in the context of the goal of simultaneously achieving the control of all therapeutic targets. SURPASS-2 Post Hoc Analysis Leite and colleagues conducted the post hoc analysis of the multicenter, randomized, parallel-group SURPASS-2 trial, involving 1879 patients with T2D that was inadequately controlled with a metformin dose of at least 1500 mg/d. In the study, patients were randomized to either tirzepatide 5 mg, 10 mg, or 15 mg vs semaglutide 1 mg. The mean age was 56.6 years, 53% were women, mean A1c was 8.3%, and mean BMI was 34.2. Patients had a median diabetes duration of 7.1 years. For the primary endpoint of the trial, the change in A1c from baseline to 40 weeks was -2.01, -2.24, and -2.30 percentage points with tirzepatide doses of 5 mg, 10 mg, and 15 mg, respectively, vs -1.86 percentage points with semaglutide, indicating that 'tirzepatide at all doses was noninferior and superior to semaglutide,' the SURPASS-2 authors reported. For the current analysis, the assessed outcomes were the attainment of standard and intensive therapeutic targets, based on the American Diabetes Association's Standards of Care in Diabetes. Specifically, standard targets include A1c < 7.0%, blood pressure < 140/90 mm Hg, low-density lipoprotein (LDL) cholesterol < 70 mg/dL, and > 10% weight loss. The intensive targets are A1c < 6.5%, blood pressure < 130/80 mm Hg, LDL cholesterol < 55 mg/dL, and > 15% weight loss. At baseline, the mean number of therapeutic targets achieved was 1.1 for standard targets and 0.5 for intensive targets, underscoring the uphill battle patients often face. Factors associated with having attained more of the goals at baseline included being White, having lower mean A1c and fasting glucose, having lower waist circumference, and having lower blood pressure levels. By the end of the study, those treated with tirzepatide at all doses achieved more of the standard goals than those treated with semaglutide (2.3, 2.5, and 2.6 with tirzepatide 5, 10, and 15 mg, respectively, vs 2.2 with semaglutide; P < .001). Likewise, the rates of achieving the intensive goals were higher with tirzepatide (1.5, 1.7, and 1.9 with tirzepatide 5, 10, and 15 mg, respectively, vs 1.3 with semaglutide; P < .001). Of note, patients on tirzepatide did not have significant differences compared with those on semaglutide in terms of the achievement of blood pressure < 140/90 mm Hg ( P = .13) or LDL cholesterol < 70 mg/dL ( P = .94). However, the rates of patients achieving three or more standard therapeutic targets were 42%, 53%, and 57% for those treated with tirzepatide at 5, 10, and 15 mg, respectively, vs 35% of those treated with semaglutide (odds ratio [OR] for pooled tirzepatide vs semaglutide, 1.91; P < .001). And for intensive targets, the corresponding rates for meeting three or more targets were 15%, 20%, and 29% for participants treated with tirzepatide at the 3 doses vs 8% for participants treated with semaglutide (OR, 3.09; P < .001). 'The most pronounced advantages of tirzepatide over semaglutide in this analysis were observed in glycemic control and weight management,' Leite said. 'Modest effects on LDL cholesterol were found with both tirzepatide and semaglutide.' Commenting on the study, Shylaja Srinivasan, MD, an associate professor of pediatrics and director of the Pediatric Type 2 Diabetes Clinic at the University of California San Francisco, said the findings are consistent with the bulk of research showing improvements with tirzepatide compared with GLP-1s. 'It is not surprising to see the findings as tirzepatide does appear to be more efficacious than semaglutide,' Srinivasan said. 'A key caveat was that the comparisons were with 1 mg of semaglutide, which is not the highest dose available,' she noted. 'A better comparison would be with the highest dose of semaglutide (2.4 mg) but that data is not available.' Nevertheless, the study's assessment of the simultaneous goals is a strength, Srinivasan said. 'This particular study looked at overall therapeutic targets, both standard and intensive, which was interesting to see compared to the usual A1c and weight only results.' The SURPASS-2 trial was funded by Eli Lilly. Leite reported having received consulting fees from BIAL. Srinivasan had no disclosures to report. Lead image: Nndanko/Dreamstime
Medscape
15-07-2025
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- Medscape
Adjuvant Triple Therapy Boosts Survival in Biliary Cancers
TOPLINE: Camrelizumab plus concurrent capecitabine and radiotherapy (combination treatment) improved overall survival (OS) and recurrence-free survival in patients with resectable extrahepatic cholangiocarcinoma (EHC) and gallbladder cancer. METHODOLOGY: Patients with EHC and gallbladder cancer have a high recurrence rate and poor survival after surgery. Existing adjuvant therapies provide limited benefit, underscoring the need for novel treatment combinations. This multicenter, randomized clinical trial investigated the safety and efficacy of chemoradiation with anti-PD-1 immunotherapy in these patients. A total of 93 patients with histologically confirmed EHC or gallbladder cancer (median age, 62 years; 52% women) who underwent curative resection with stage pT2-4 or N1M0 disease were randomly assigned to either the combination treatment group (n = 46) or the observation group (no anticancer treatment unless relapse was detected; n = 47). Those in the combination treatment group received 200 mg camrelizumab intravenously every 3 weeks, followed by concurrent 1330 mg/m 2 oral capecitabine twice daily with radiotherapy (45 Gy in 25 fractions for lymph nodes and 52.5-55.0 Gy for tumor beds). oral capecitabine twice daily with radiotherapy (45 Gy in 25 fractions for lymph nodes and 52.5-55.0 Gy for tumor beds). The primary endpoint was OS, and secondary endpoints were recurrence-free survival and adverse events (AEs). The median follow-up duration was 36 months. TAKEAWAY: The combination treatment significantly improved OS (hazard ratio [HR], 0.43; P = .004), with 3-year OS rate of 58.2% vs 30.5% in the observation group. The median recurrence-free survival was longer in the combination treatment group than in the observation group (26 months vs 13 months; HR, 0.46; P < .001), with the 3-year recurrence-free survival rate of 40.3% vs 17.2%. No treatment-related deaths were observed. The most common severe AEs of grade 3 or 4 were anemia (15%), radiation-associated dermatitis (11%), nausea (11%), and hand-foot syndrome (4%) in the combination group and anemia (4%), fatigue (4%), and neutropenia (4%) in the observation group. Subgroup analyses suggested patients with EHC vs gallbladder cancer and those with an Eastern Cooperative Oncology Group score of 0 and tumors ≤ 5 cm were more likely to benefit from the combination treatment. IN PRACTICE: 'We congratulate the authors for conducting and reporting an important clinical trial that moves the field forward. Considering the current level of evidence used to guide patient management after resection, we suspect this regimen may be adopted into practice even prior to the conduct of a phase 3 trial,' Edgar Ben-Josef, MD, University of Pennsylvania, Philadelphia, wrote, in an invited commentary on the new research published in JAMA Oncology. 'However, we would caution that this study should be viewed not as an ending but as a building block toward studies that demonstrate an even greater level of confidence [in] more effective adjuvant regimens for patients with biliary cancers. SOURCE: The study, led by Han Xiao, MD, The First Affiliated Hospital of Sun Yat-sen University in Guangzhou, China, was published online in JAMA Oncology. LIMITATIONS: This study was only conducted on Chinese patients, limiting generalizability to Western populations. Although the study met the predefined 2-year follow-up for all patients, both groups showed better-than-expected OS rates, resulting in fewer endpoint events than anticipated. Additionally, the open-label design and the combination of multiple treatments might have confounded efficacy assessment for each treatment component. DISCLOSURES: This study received project grants from the National Natural Science Foundation of China and the Science and Technology Program of Guangzhou. The authors reported having no relevant conflicts of interest. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
25-06-2025
- Health
- Medscape
Mindfulness and Tai Chi Improve Mood in Cancer Survivors
TOPLINE: Both Mindfulness-Based Cancer Recovery (MBCR) and Tai Chi/Qigong (TCQ) significantly improved mood in survivors of cancer, whether participants selected their preferred program or were randomly assigned to either type of program. MBCR had greater benefits in reducing tension and anger, while TCQ was particularly effective in reducing depression and boosting vigor. METHODOLOGY: Prior studies have shown that MBCR and TCQ can reduce distress and psychosocial symptoms in patients with cancer, but comparisons have largely been with usual care rather than active control individuals. Researchers conducted a pragmatic, preference-based, multisite randomized controlled design trial to compare these mind-body therapies. A total of 587 distressed survivors of cancer (average age, 60.7 years; 75% women), irrespective of the stage and type of cancer, were enrolled. Participants with a preference for either MBCR or TCQ received their preferred intervention (n = 376) and were then randomly assigned to either the immediate or waitlisted group in a 2:1 ratio. Those without a preference were randomly assigned (1:1) to either intervention (n = 211) and then to the immediate or waitlist group in a 2:1 ratio. Participants received MBCR as a standard 9-week program of weekly in-person group meetings of 1 hour 45 minutes, along with a 6-hour weekend retreat on a Saturday between weeks 6 and 7. TCQ was offered as an 11-week program consisting of a 1.5-hour weekly group meeting and a 4-hour weekend retreat. The primary outcome was change in total mood disturbance, measured by the Profile of Mood States, which included tension-anxiety, depression, anger-hostility, and vigor-activity subscales. TAKEAWAY: In the random assignment group, total mood disturbance scores decreased significantly in both the immediate MBCR (19.9 at baseline to 12.5 after treatment) and immediate TCQ (17.7 at baseline to 12.0 after treatment) groups compared with that in the waitlist control group (P for interaction = .03 and.07, respectively). In the preference group, although total mood disturbance scores decreased in both the immediate MBCR and TCQ groups, the interaction effect relative to the waitlist control group was not significant (P = .57 and P = .09, respectively). Participants who received MBCR showed greatest improvements in tension, anger, and vigor scores, whereas those who received TCQ showed greatest improvements in anger, depression, and vigor scores. A combined analysis of the immediate vs waitlist groups showed substantial reductions in total mood disturbance scores with MBCR (estimate, -4.15; P = .10) and significant reductions in the scores with TCQ (estimate, -5.13; P = .01). IN PRACTICE: 'Both MBCR and TCQ proved beneficial for improving overall mood in a broad swath of people living with cancer of different types and stages after treatment completion who were experiencing significant distress,' the authors wrote. SOURCE: The study, led by Linda E. Carlson, PhD, University of Calgary in Calgary, Alberta, Canada, was published online in Journal of Clinical Oncology. LIMITATIONS: Potential baseline imbalances existed between participants who chose MBCR vs TCQ or who chose to be randomly assigned. The study design required participants to have sufficient mobility, time, and energy to travel to program venues, which may have excluded some eligible candidates. Additionally, some discrepancies in dropout rates were observed across groups, although these did not violate missing at random data analytic assumptions. DISCLOSURES: This study was funded by grants from the Lotte & John Hecht Memorial Foundation and Enbridge Research Chair for Psychosocial Oncology. Three authors reported having ties with various sources. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
