Pembrolizumab Added to Chemotherapy Improves Survival in Advanced Esophageal Cancer

Treatment of esophagogastric cancer has evolved with approval of immune checkpoint inhibitors to combine with first-line chemotherapy. The benefit of these agents may depend on expression of the target, PD-L1.

Investigators report results of KEYNOTE-590, an industry-sponsored, international, placebo-controlled, double-blind, phase 3 trial comparing chemotherapy with infusional 5-FU and cisplatin with or without the addition of pembrolizumab in advanced esophageal squamous cell carcinoma (SCC) or adenocarcinoma. Of 749 patients, 54% were from Asia, 73% had SCC, and 51% had PD-L1 combined positive scores (CPS) ≥10%.

The dual primary endpoints of improved overall survival (OS) in patients with SCC and CPS ≥10% and improved OS and progression-free survival (PFS) in patients with SCC, patients with CPS ≥10%, and all patients randomized were met. At a median follow up of 22.6 months, OS was superior with the addition of pembrolizumab in patients with SCC and CPS ≥10% (13.9 vs. 8.8 months, hazard ratio, 0.57; P<0.0001), and both OS and PFS were superior (P≤0.006) with pembrolizumab in patients with SCC (OS, 12.6 vs. 9.8 months; PFS, 6.3 vs 5.8 months), patients with CPS ≥10% (OS, 13.5 vs. 9.4 months; PFS, 7.5 vs. 5.5 months), and all patients (OS, 12.4 vs. 9.8 months; PFS, 6.3 vs. 5.8 months).

Among patients with adenocarcinoma, OS was also longer with pembrolizumab (11.6 vs. 9.9 months). Among all randomized patients, the OS benefit was diminished in those with CPS <10% (HR, 0.86) compared to CPS ≥10% (HR, 0.62). Rate and duration of response were also improved with pembrolizumab. There were no new safety signals, and rates of grade 3 and 4 treatment-related adverse events were similar with and without pembrolizumab (68%–72%).