The results of KEYNOTE-062 randomised phase III trial were presented at 2019 ASCO Annual Meeting by Dr Josep Tabernero of Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain. Dr Tabernero told delegates that the study achieved its primary endpoint, showing that for patients with PD-L1-positive, HER2-negative, advanced gastric or gastro-oesophageal junction cancer, front-line therapy with pembrolizumab resulted in non-inferior overall survival (OS) when compared to standard chemotherapy. Pembrolizumab showed clinically meaningful improvement in OS among patients with tumours that had high levels of PD-L1 expression. The study also evaluated combined treatment with pembrolizumab and standard chemotherapy, but this regimen did not improve survival relative to chemotherapy alone.
The KEYNOTE062 (NCT02494583) was a randomised, active controlled study of first-line pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy in patients with tumours with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced gastric cancer. Randomisation was stratified by region, disease status, and fluoropyrimidine treatment.
Primary endpoints were OS in CPS ≥1 and CPS ≥10 for pembrolizumab plus chemotherapy versus chemotherapy and pembrolizumab versus chemotherapy and progression-free survival (PFS) according RECIST v1.1, central review in CPS ≥1 for pembrolizumab plus chemotherapy versus chemotherapy. The overall response rate (ORR) according RECIST v1.1, central review in CPS ≥1 for pembrolizumab plus chemotherapy versus chemotherapy was the secondary endpoint.
In total 763 patients from whom 281 with CPS ≥10 were randomised to pembrolizumab plus chemotherapy (257), pembrolizumab (256), or chemotherapy (250). Median age was 62 years and 26% had previous gastric surgery. Around 69% of patients were diagnosed with gastric cancer and 30% with gastro-oesophageal cancer. Median follow-up was 11.3 months.
Pembrolizumab was noninferior to chemotherapy for OS in CPS ≥1 per prespecified margins. Pembrolizumab versus chemotherapy prolonged OS in CPS ≥10; median 17.4 vs 10.8 months, HR 0.69. Pembrolizumab plus chemotherapy versus chemotherapy was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for pembrolizumab plus chemotherapy.
Pembrolizumab plus chemotherapy did not significantly prolong PFS in CPS ≥1.
The ORR was higher for pembrolizumab plus chemotherapy versus chemotherapy.
Grade 3-5 drug-related adverse events rates were 17% in pembrolizumab arm, 73% in pembrolizumab plus chemotherapy arm, and 69% in chemotherapy arm.
The authors concluded that as first-line therapy for advanced gastric cancer, pembrolizumab was noninferior to chemotherapy for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. Pembrolizumab plus chemotherapy did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10.
The safety profile was more favorable for pembrolizumab versus chemotherapy.
The investigators are currently analyzing subsets of the data to determine who benefited most in terms of response to pembrolizumab alone or to its combination with chemotherapy. The study team is also analyzing the effectiveness of the treatment based on pre-specified geographical regions. In particular, the study enrolled 58% of patients from North America, Europe, and Australia; 25% from Asia; and 17% from other regions of the world.
The study was funded by Merck & Co., Inc.
Tabernero J, Van Cutsem E, Bang Y-J, et al. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. J Clin Oncol 37, 2019 (suppl; abstr LBA4007).