Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study.

Abstract

LBA4007 Background: KEYNOTE062 (NCT02494583) was a randomized, active controlled study of 1L P or P+C vs C in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced GC. Methods: Eligible pts were randomized 1:1:1 to P 200 mg Q3W for up to 2 y, P+C (cisplatin 80 mg/m2 + 5-FU 800 mg/m2/d on d1-d5 Q3W [or capecitabine 1000 mg/m2 BID on d1-d14 Q3W per local guideline]) or placebo Q3W + C. Randomization was stratified by region, disease status, and fluoropyrimidine treatment. Primary endpoints were OS in CPS ≥1 and CPS ≥10 for P+C vs C and P vs C and PFS (RECIST v1.1; central review) in CPS ≥1 for P+C vs C. ORR (RECIST v1.1; central review) in CPS ≥1 for P+C vs C was the secondary endpoint. Final analysis cutoff date was 26 Mar 2019. Results: 763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (Table). Median follow-up was 11.3 mo. P was noninferior to C for OS in CPS ≥1 per prespecified margins. P vs C prolonged OS in CPS ≥10 (median 17.4 vs 10.8 mo; HR 0.69; 95% CI 0.49-0.97) but wasn’t tested per analysis plan. P+C vs C was not superior for OS in CPS ≥1 or CPS ≥10, with a favorable trend for P+C. P+C did not significantly prolong PFS in CPS ≥1. ORR was higher for P+C vs C. Grade 3-5 drug-related AE rates were 17% (P), 73% (P+C), and 69% (C). Conclusions: As 1L therapy for advanced GC, P was noninferior to C for OS in CPS ≥1 with clinically meaningful improvement for OS in CPS ≥10. P+C did not show superior OS and PFS in CPS ≥1 and OS in CPS ≥10. The safety profile was more favorable for P vs C. Clinical trial information: NCT02494583. [Table: see text]

Tumor immune response and immunotherapy in gastric cancer

“…However, pembrolizumab had a better safety profile than paclitaxel. The phase 3 KEYNOTE-062 trial enrolled 763 patients with PD-L1-positive, HER2-negative, advanced G/GEJ cancer; pembrolizumab used as a first-line therapy resulted in noninferior OS compared with standard chemotherapy [52]. Additionally, pembrolizumab showed significant improvement in OS among patients that had tumors with PD-L1 CPS ≥ 10.…”

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

“…A superior and clinically meaningful benefit by improvement of OS, however, was seen in patients with high programmed cell death receptor ligand 1 expressing tumours of combined positive score ≥10 (median OS 17.4 vs. 10.8 months; HR 0.69, 95% CI 0.49-0.97), but this was not analysed for statistical significance due to the study's hierarchical design. Surprisingly, the combination of the checkpoint inhibitor with chemotherapy was not superior for OS, neither in combined positive score ≥1 nor in combined positive score ≥10 tumours when compared to chemotherapy alone, but showed a favourable trend for the combination (median OS in patients with CPS ≥ 10: with combination immunochemotherapy 12.3 vs. 10.8 months with chemotherapy; HR 0.85, 95% CI 0.62-1.17; p = 0.158) [15]. As observed in several other immune checkpoint inhibition trials, the rates of serious side effects were lowest among patients treated with pembrolizumab alone.…”

“…Since the results of nivolumab and pembrolizumab in the late line of treatment were promising, these agents are tested in a first line setting in combination with standard chemotherapy regimens in the still ongoing CHECKMATE-649 and the KEYNOTE-062 study, respectively [14,15].…”

Molecular profiling in gastroesophageal cancer—clinical routine and future perspective

“…However, in the Keynote-181 trial, pembrolizumab was demonstrated to be effective in both adenocarcinoma and squamous cell carcinoma in second line, when CPS was ≥10% [20]. The Keynote-62 trial was presented within the ASCO 2019 [21]. The results of this study, which tested pembrolizumab as first-line treatment in advanced and metastasized gastroesophageal cancer, might indicate a survival benefit of patients with a CPS ≥10%.…”