Table 2 Summary of the key phase III clinical trials of ICIs in metastatic GC
From: Gastric cancer treatment: recent progress and future perspectives
Therapy line | Trial | Agent | Experimental arm | Control arm | Primary endpoints | Result (Experimental vs. Control) | References |
|---|---|---|---|---|---|---|---|
First line (HER2-negative) | KEYNOTE-062 | Pembrolizumab | Pembrolizumab monotherapy; Pembrolizumab plus chemotherapy (PF or XP) | Chemotherapy (PF or XP) | OS and PFS in pts with CPS ≥ 1 | Pembro vs. Chemo: OS: 10.6 vs. 11.1 months (HR, 0.91; 99.2% CI, 0.69–1.18); PFS: 2.0 vs. 6.4 months (HR, 1.66; 95% CI, 1.37–2.01); Pembro + chemo vs. Chemo: OS: 12.5 vs. 11.1 months (HR, 0.85; 95% CI, 0.70–1.03); PFS: 6.9 vs. 6.4 months (HR, 0.84; 95% CI, 0.70–1.02) | |
|  | CheckMate-649 | Nivolumab | Nivolumab plus chemotherapy (XELOX or FOLFOX) | Chemotherapy (XELOX or FOLFOX) | OS and PFS in pts with CPS ≥ 5 | Nivo + chemo vs. Chemo: OS: 14.4 vs. 11.1 months (HR 0.71; 98.4% CI, 0.59–0.86); PFS: 7.7 vs. 6.05 months (HR 0.68; 98% CI, 0.56–0.81); Nivo + ipi vs. Chemo: OS: 11.2 vs. 11.6 months (HR, 0.89; 95% CI, 0.71–1.10); PFS: 2.8 vs. 6.3 months (HR, 1.42; 95% CI, 1.42–1.76) | |
|  | ATTRACTION-4 | Nivolumab | Nivolumab plus chemotherapy (SOX or CAPOX) | Chemotherapy (SOX or CAPOX) | OS and PFS | OS: 17.45 vs. 17.15 months (HR 0·90; 95% CI 0·75–1·08); PFS: 10.45 vs. 8.34 months (HR 0·68; 98·51% CI 0·51–0·90) | [58] |
|  | ORIENT-16 | Sintilimab | Sintilimab plus chemotherapy (CapeOX) | Chemotherapy (CapeOX) | OS in pts with CPS ≥ 5 | OS: 18.4 vs. 12.9 months (HR 0.660; 95% CI 0.505–0.864); | [59] |
|  | RATIONALE-305 | Tislelizumab | Tislelizumab plus chemotherapy (XELOX or PF) | Chemotherapy (XELOX or PF) | OS and PFS | In the PD-L1 + (i.e., PD-L1 TAP score ≥ 5%) population: OS: 17.2 vs. 12.6 months (HR 0·74; 95% CI 0·59–0·94); PFS: 7.2 vs. 5.9 months (HR 0·67; 95% CI 0·55–0·83) | |
|  | KEYNOTE-859 | Pembrolizumab | Pembrolizumab plus chemotherapy (CAPOX or PF) | Chemotherapy (CAPOX or PF) | OS | OS: 12.9 vs. 11.5 months (HR 0·78; 95% CI 0·70–0·87); PFS: 6.9 vs. 5.6 months (HR 0·76; 95% CI 0·67–0·85) | [55] |
|  | JAVELIN Gastric 100 | Avelumab | Avelumab maintenance after 12 weeks of 1st-line chemotherapy (FOLFOX) | Continued chemotherapy (FOLFOX) | OS | OS: 10.4 vs. 10.9 months (HR 0.91; 95% CI, 0.74–1.11) | |
First line (HER2-positive) | KEYNOTE-811 | Pembrolizumab | Pembrolizumab plus trastuzumab and chemotherapy (XELOX or PF) | Trastuzumab plus chemotherapy (XELOX or PF) | OS and PFS | ORR (74.4% vs. 51.9%); results of PFS and OS are immature | [73] |
Sencond line | KEYNOTE-061 | Pembrolizumab | Pembrolizumab | Chemotherapy (paclitaxel) | OS and PFS in pts with CPS ≥ 1 | OS: 9.1 vs. 8.3 months (HR 0·82; 95% CI 0·66–1·03); PFS: 1.5 vs. 4.1 months ((HR 1·27, 95% CI 1·03–1·57) | [84] |
Third line | ATTRACTION-2 | Nivolumab | Nivolumab | Placebo | OS | OS: 5.3 vs. 4.1 months (HR 0·63, 95% CI 0·51–0·78) | [64] |
|  | JAVELIN Gastric 300 | Avelumab | Avelumab | Chemotherapy (paclitaxel or irinotecan) | OS | OS: 4.6 vs. 5.0 months (HR 1.1, 95% CI 0·9–1.4) | [65] |