Shitara K, et al. - Pembrolizumab was compared to paclitaxel in patients with advanced gastric or gastro-esophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine in this randomized, open-label, phase 3 study performed at 148 medical centers in 30 countries. Outcomes revealed no significant improvement in overall survival with pembrolizumab when compared with paclitaxel as second-line therapy for advanced gastric or gastro-esophageal junction cancer with PD-L1 CPS of 1 or higher. Relative to paclitaxel, pembrolizumab displayed a better safety profile.

Methods

• Researchers randomized eligible patients (1:1) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel.
• Overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher as were primary endpoints.
• In all patients, safety was assessed irrespective of CPS.
• For overall survival, the significance threshold was p=0·0135 (one-sided).

Results

• Researchers enrolled 592 patients from June 4, 2015 to July 26, 2016.
• They identified 395 patients who had a PD-L1 CPS of 1 or higher; of these, 196 were assigned to receive pembrolizumab and 199 were assigned to receive paclitaxel.
• Death was reported for 326 patients in the population with CPS of 1 or higher up to October 26, 2017, (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group).
• With pembrolizumab and paclitaxel, median overall survival was 9.1 months (95% CI 6.2–10.7) and 8.3 months (7.6–9.0), respectively (hazard ratio [HR] 0.82, 95% CI 0.66–1.03; one-sided p=0.0421).
• Findings showed median progression-free survival of 1.5 months (95% CI 1.4–2.0) and 4.1 months (3.1–4.2) with pembrolizumab and paclitaxel, respectively (HR 1.27, 95% CI 1.03–1.57).
• Grade 3–5 treatment-related adverse events were reported in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel in the total population.