The most trusted, influential source of new medical knowledge and clinical best practices in the world.įirst-line chemotherapy for advanced esophageal squamous-cell carcinoma results in poor outcomes. Information and tools for librarians about site license offerings. Valuable tools for building a rewarding career in health care. The authorized source of trusted medical research and education for the Chinese-language medical community.
The most advanced way to teach, practice, and assess clinical reasoning skills. Information, resources, and support needed to approach rotations - and life as a resident. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. NEW! Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery.Ĭoncise summaries and expert physician commentary that busy clinicians need to enhance patient care. These results support adjuvant nivolumab as a standard-of-care treatment for patients with high-risk MIUC after radical surgery.NEW! A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. NUTRFS and DMFS were also improved with nivolumab compared with placebo in both ITT patients and those with PD-L1 ≥1%. DFS benefit was observed in most prespecified subgroups. With longer follow-up, nivolumab continued to demonstrate clinically meaningful improvement in DFS versus placebo for patients with high-risk MIUC after radical surgery, both in ITT patients and in patients with PD-L1 ≥1%. NUTRFS and DMFS were also improved with nivolumab versus placebo in both ITT patients and those with PD-L1 ≥1% ( Table). Improvement in DFS was observed with nivolumab versus placebo for most subgroups analyzed, including age, sex, ECOG PS, nodal status, use of prior cisplatin-based chemotherapy, and PD-L1 status. Among patients with PD-L1 ≥1%, DFS probability at 12 months was 67.6% with nivolumab and 46.3% with placebo. DFS probability at 12 months was 63.5% with nivolumab and 46.9% with placebo in ITT patients. With 5 months additional follow-up, DFS benefit with nivolumab versus placebo was maintained in ITT patients (minimum follow-up, 11.0 months median follow-up, 24.4 months and 22.5 months ) and patients with PD-L1 ≥1% (minimum follow-up, 11.4 months median follow-up, 25.5 months and 22.4 months Table). Overall, 353 patients were randomized to nivolumab (PD-L1 ≥1%, n=140) and 356 to placebo (PD-L1 ≥1%, n=142). Distant metastasis-free survival (DMFS) was an exploratory endpoint. Non–urothelial tract recurrence-free survival (NUTRFS) in ITT patients and in patients with PD-L1 ≥1% was a secondary endpoint. DFS was also evaluated in prespecified subgroups. Primary endpoints were DFS in all randomized patients (ITT population) and in patients with PD-L1 ≥1%. Patients had radical surgery within 120 days ± neoadjuvant cisplatin or were ineligible/declined cisplatin-based chemotherapy, had evidence of urothelial carcinoma at high risk of recurrence per pathologic staging, were disease-free by imaging, and had Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1. Patients were randomized 1:1 to nivolumab 240 mg intravenously Q2W or placebo for ≤1 year of adjuvant treatment, and stratified by nodal status, prior neoadjuvant cisplatin, and PD-L1 status. We report DFS outcomes with longer follow-up.ĬheckMate 274 is a phase 3, randomized, double-blind, multicenter trial of nivolumab (anti-PD-1 antibody) versus placebo in high-risk MIUC (bladder, ureter, renal pelvis) after radical surgery. In the CheckMate 274 trial of adjuvant nivolumab versus placebo in patients with MIUC at high risk of recurrence after radical surgery (minimum follow-up in the intention-to-treat population: 5.9 months), disease-free survival (DFS) was significantly improved with nivolumab versus placebo both in the ITT population (HR, 0.70 98.22% CI, 0.55-0.90 P<0.001) and in the population with tumor PD-L1 expression ≥1% (HR, 0.55 98.72% CI, 0.35-0.85 P<0.001). Furthermore, some patients are ineligible or decline cisplatin-based chemotherapy. There is an unmet need in this population as no evidence supports adjuvant chemotherapy in patients after NAC and the level of evidence is low for patients who have not received NAC (except for urothelial carcinoma of the renal pelvis and ureter). The standard of care for muscle-invasive urothelial carcinoma (MIUC) is surgery ± cisplatin-based neoadjuvant chemotherapy (NAC), although >50% of patients experience metastatic recurrence.
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