![]() ![]() Mok, MD, of the State Key Laboratory of South China, Chinese University of Hong Kong, is the corresponding author for The Lancet article.ĭisclosure: The study was funded by Merck Sharp & Dohme. The investigators concluded, “The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non–small cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS.” Grade ≥ 3 immune-mediated events occurring in ≥ 5 patients in the pembrolizumab group were pneumonitis (3%), severe skin reactions (2%), and hepatitis (1%). Immune-mediated adverse events or infusion reactions occurred in 28% (8% grade ≥ 3 ) vs 7% (1% grade ≥ 3). Death was considered related to treatment in 2% vs 2% of patients. Treatment-related adverse events led to treatment discontinuation in 9% vs 9% of patients. Grade ≥ 3 treatment-related adverse events occurred in 18% vs 41%, with those occurring in ≥ 20 patients being pneumonitis (3%) in the pembrolizumab group and anemia (13%), decreased neutrophil count (9%), neutropenia (7%), decreased white blood cell count (5%), and decreased platelet count (3%) in the chemotherapy group. Treatment-related adverse events of any grade occurred in 63% of the pembrolizumab group vs 90% of the chemotherapy group. At least 1 subsequent anticancer therapy was received by 38% of the pembrolizumab group and 44% of the chemotherapy group, including immunotherapy in 3% and 20%, respectively. Median progression-free survival durations in the 3 TPS populations were 7.1 months vs 6.4 months, 6.2 months vs 6.6 months, and 5.4 months vs 6.5 months (significance not formally tested in ≥ 20% or ≥ 1% population, since the superiority boundary was not met in ≥ 50% population). Objective response rates in the 3 TPS populations were 39% vs 32%, 33% vs 29%, and 27% vs 27%, with median durations of response of 20.2 months in the pembrolizumab group in all TPS populations vs 10.8, 8.3, and 8.3 months in the chemotherapy group. Hazard ratios favored pembrolizumab in most subgroups in the three TPS populations. In an exploratory analysis, the hazard ratio for pembrolizumab vs chemotherapy was 0.82 (95% confidence interval = 0.77–1.11) among patients with a TPS of 1% to 49% (median = 13.4 months vs 12.1 months). Median overall survival in the pembrolizumab vs chemotherapy group was 20.0 months vs 12.2 months among patients with a TPS ≥ 50% (hazard ratio = 0.69, P =. 0124, respectively) in the intention-to-treat population, assessed sequentially if findings in the previous TPS population were significant. Primary endpoints were overall survival in patients with TPS ≥ 50%, ≥ 20%, and ≥ 1% (one-sided significance thresholds of P =. ![]() Randomization was stratified by region (East Asia vs rest of world), Eastern Cooperative Oncology Group performance status (0 vs 1), histology (squamous vs nonsquamous), and PD-L1 TPS (≥ 50% vs 1%–49%). Maintenance therapy with pemetrexed at 500 mg/m² every 3 weeks was optional but encouraged in chemotherapy group patients with nonsquamous histology. Patients were randomly assigned between December 2014 and March 2017 to receive pembrolizumab at 200 mg every 3 weeks for up to 35 cycles (n = 637) or investigator’s choice of platinum-based chemotherapy (carboplatin AUC of 5–6 plus paclitaxel at 200 mg/m² or pemetrexed at 500 mg/m² every 3 weeks for 4 to 6 cycles ). The open-label trial included 1,274 patients from 213 sites in 32 countries with PD-L1 TPS ≥1%. ![]() The study supported the April 11th expansion of the indication for pembrolizumab in this setting from a TPS threshold of ≥ 50% in patients with metastatic disease to ≥ 1% expression in patients with stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, and patients with metastatic NSCLC.
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