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Pembrolizumab with or without chemotherapy versus chemotherapy for first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The Phase 3 KEYNOTE-062 Study
KEYNOTE062 (NCT02494583) was a randomized, active controlled study of first-line (1L) pembrolizumab (P) or pembrolizumab plus chemotherapy (P+C) vs chemotherapy (C) in pts with PD-L1 combined positive score ≥1 (CPS ≥1), HER2-negative, advanced gastric cancer (GC).
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.
763 pts (281 with CPS ≥10) were randomized to P+C (257), P (256), or C (250) (
| CPS ≥1 | P+C | C | P | C |
|---|---|---|---|---|
| aMedian, mo (95% CI) | N = 257 | N = 250 | N = 256 | N = 250 |
| OSa | 12.5 (10.8-13.9)/ 11.1 (9.2-12.8) | 10.6 (7.7-13.8)/11.1 (9.2-12.8) | ||
| HR (95% CI)/ b99.2% CI | 0.85 (0.70, 1.03) | 0.91 (0.74-1.10) | ||
| 0.91b (0.69-1.18); NI margin = 1.2 | ||||
| PFSa | 6.9 (5.7-7.3)/ 6.4 (5.7-7.0) | 2.0 (1.5-2.8)/6.4 (5.7-7.0) | ||
| HR (95% CI) | 0.84 (0.70-1.02); |
1.66 (1.37-2.01) | ||
| ORR, % (95% CI) | 48.6 (42.4-54.9)/36.8 (30.8-43.1) | 14.5 (10.4-19.4)/36.8 (30.8-43.1) | ||
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| OSa | 12.3 (9.5-14.8)/10.8 (8.5-13.8) | 17.4 (9.1-23.1)/10.8 (8.5-13.8) | ||
| HR (95% CI) | 0.85 (0.62-1.17); |
0.69 (0.49-0.97) | ||
| PFSa | 5.7 (5.5-8.2)/6.1 (5.3-6.9) | 2.9 (1.6-5.4)/6.1 (5.3-6.9) | ||
| ORR, % (95% CI) | 52.5 (42.2-62.7)/36.7 (26.8-47.5) | 25.0 (16.6-35.1)/36.7 (26.8-47.5) | ||
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.
