As reported in The Lancet by Shitara et al, the phase III KEYNOTE-061 trial showed no significant overall survival benefit with pembrolizumab vs paclitaxel in patients with advanced gastric or gastroesophageal junction cancer progressing on platinum-fluoropyrimidine treatment with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) of ≥ 1.
In the open-label trial, 592 patients from 148 sites in 30 countries were enrolled between June 2015 and July 2016 and randomized to receive pembrolizumab 200 mg every 3 weeks for up to 2 years (n = 296) or paclitaxel 80 mg/m2 on days 1, 8, and 15 of 4-week cycles (n = 296). Of 395 patients with PD-L1 CPS ≥ 1, 196 patients were randomized to receive pembrolizumab and 199 to receive paclitaxel.
The primary endpoints were overall survival and progression-free survival in patients with PD-L1 CPS ≥ 1. The significance threshold for overall survival was P = .0135 (one-sided). Safety was assessed in all patients. Overall, 63% to 64% of patients were from Europe, Israel, North America, and Australia, and 30% were from Asia.
Overall and Progression-Free Survival
As of data cutoff in October 2017, median follow-up was 8.5 months among patints with PD-L1 CPS ≥ 1. Death had occurred in 77% of patients in the pembrolizumab group and 88% of patients in the paclitaxel group. Median overall survival was 9.1 months vs 8.3 months (hazard ratio [HR] = 0.82, one-sided P = .0421). Survival was 40% vs 27% at 12 months and 26% vs 15% at 18 months. Median progression-free survival was 1.5 months vs 4.1 months (HR = 1.27, 95% confidence interval = 1.03–1.57). Rates of confirmed response were 16% vs 14%; median durations of response were 18.0 vs 5.2 months. Among patients with PD-L1 CPS < 1, median overall survival was 4.8 months vs 8.2 months (HR = 1·20, 95% CI = 0.89–1.63).
In the total population, grade ≥ 3 treatment-related adverse events occurred in 14% of the pembrolizumab group and 35% of the paclitaxel group; the most common were anemia (2%) and fatigue (2%) in the pembrolizumab group and decreased neutrophil count (10%) and neutropenia (7%) in the paclitaxel group. Treatment-related adverse events led to study drug discontinuation in 3% vs 5% of patients. Adverse events considered to be immune-related occurred in 18% vs 8% of patients. Those of grade ≥ 3 in the pembrolizumab group included hepatitis in 4 patients (1%), hypophysitis in 2 (< 1%), and pneumonitis in 2 (< 1%).
The investigators noted that Kaplan-Meier survival curves favored paclitaxel for the first 8 months after randomization. After crossing at 8 months, a separation of curves favoring pembrolizumab was maintained, potentially reflecting durability of benefit in patients with response or prolonged stable disease. The pembrolizumab curve appeared to plateau at about 20 months, suggesting long-term benefit in some patients.
They concluded, “Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing.”
The study was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co.
Kohei Shitara, MD, of the National Cancer Center Hospital East, Kashiwa, is the corresponding author for The Lancet article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.