PS3 KEYNOTE-024 Update: Pembrolizumab Vs Platinum-Based Chemotherapy for Advanced NSCLC with PD-L1 Tumor Proportion Score ≥50%
Journal of thoracic oncology(2018)
摘要
KEYNOTE-024 (NCT02142738) is a multicenter, international, phase 3, randomized, open-label trial of first-line pembrolizumab vs platinum-based chemotherapy for patients with advanced non–small-cell lung cancer (NSCLC; any histology) with PD-L1 tumor proportion score (TPS) ≥50% and without EGFR/ALK alterations. The primary analysis of KEYNOTE-024 showed significantly improved PFS (HR=0.50; P<0.001) and OS (HR=0.60; P=0.005) with fewer treatment-related AEs with pembrolizumab compared with chemotherapy after a median follow-up of 11.2 months. We report on updated results after a median follow-up of 25.2 months. Patients were randomized to pembrolizumab 200 mg every 3 weeks (35 cycles) or 4–6 cycles of investigator's choice of carboplatin/cisplatin + gemcitabine, carboplatin + paclitaxel, or carboplatin/cisplatin + pemetrexed with optional pemetrexed maintenance (for nonsquamous histology). Randomization was stratified by ECOG PS (0 vs 1), histology (squamous vs nonsquamous), and geographic region (East Asia vs non–East Asia). Treatment continued until disease progression per RECIST version 1.1, intolerable toxicity, or withdrawal of consent. Patients in the chemotherapy arm could cross over to receive pembrolizumab monotherapy upon disease progression. Response was assessed every 9 weeks per RECIST version 1.1 by blinded independent central review (stopped after the second interim analysis) and by investigator assessment. PFS was the primary endpoint; OS and safety were secondary endpoints. 305 patients were enrolled (pembrolizumab, n=154; chemotherapy, n=151). At data cutoff (July 10, 2017), 73 patients (47.4%) randomized to pembrolizumab and 96 patients (63.6%) randomized to chemotherapy had died. The hazard ratio (HR) for OS was 0.63 (95% confidence interval [CI], 0.47–0.86; nominal P=0.002). Median (95% CI) OS was 30.0 (18.3–not reached) months for pembrolizumab and 14.2 (9.8–19.0) months for chemotherapy. Estimated 12-month OS was 70.3% (95% CI, 62.3%–76.9%) for pembrolizumab and 54.8% (95% CI, 46.4%–62.4%) for chemotherapy. 82 patients allocated to the chemotherapy arm crossed over to receive pembrolizumab upon meeting eligibility criteria. Treatment-related AEs were less frequent with pembrolizumab than with chemotherapy (76.6% vs 90.0%, respectively) as were treatment-related grade 3–5 AEs (31.2% vs 53.3%). With prolonged follow‒up, first-line pembrolizumab monotherapy remains superior to platinum-based chemotherapy despite crossover from chemotherapy to an anti‒PD-1 agent.
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关键词
pembrolizumab,nonesmall-cell lung cancer,overall survival,KEYNOTE-024
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