Table 1.
Practice-changing Phase 3 trials in advanced gastro-oesophageal cancer involving immune checkpoint inhibitors.
| Trial | Phase | Population | Setting | Agent | Response rate | PFS | OS |
|---|---|---|---|---|---|---|---|
| >2nd line | |||||||
| ATTRACTION-2 Kang at al.34 | 3 | Advanced GOJ or GC (n = 493) Asian population | ≥2nd line | Nivolumab (n = 330) vs placebo (n = 163) | 11% (8–16%) DCR 40% (34–46%) | 1.61 m (1.5–2.3) | 5.3 m vs 4.1 m (HR 0.63, P < 0.0001) |
| KEYNOTE-059 (cohort 1) Fuchs et al.28 | 2 | GC/GOJ (n = 259) | ≥2nd line | Pembrolizumab (all patients) | 12%8–17 PD-L1 + ve 16% PD-L1 –ve 6% DCR 2722–33 | 2.0 m (2.0–2.1) | 5.5 m (4.2–6.5) |
| CHECKMATE-032 Janjigian et el.37 | 1/2 | Advanced OC, GOJ or GC (n = 160) | ≥2nd line | Nivolumab 3 mg/kg (n = 59) nivolumab 1 mg/kg + Ipilimumab 3 mg/kg (n = 49) nivolumab 3 mg/kg + Ipilimumab 1 mg/kg (n = 52) | 12% vs 24% vs 8% | 12 month: 8% vs 17% vs 10% | 12 month: 39% vs 35% vs 24% |
| JAVELIN-300 Bang et al.120 | 3 | GOJ (n = 111) or GC (n = 260) | 3rd line | Avelumab vs TPC | 2.2% vs 4.3% DCR 22.2 vs 44.1% | 1.4 m vs 2.7 m | 4.6 m vs 5.0 m (HR 1.1, NS) |
| 2nd line | |||||||
| KEYNOTE-061 Shitara et al.17 | 3 | GOJ (n = 185) or GC (n = 407) | 2nd line | Pembrolizumab (n = 296) vs paclitaxel (n = 296) | CPS ≥ 1: 16% vs 14% CPS ≥ 10: 24.5% v 9.1% CPS < 1: 2% vs 10.4% | 1.5 m vs 4.1 m (HR 1.27) CPS < 1: HR 2.05 | 9.1 m vs 8.3 m (HR 0.82, P = 0.0421) CPS ≥ 10: 10.4 m v 8.0 m (HR 0.64) CPS < 1: 4.8 m vs 8.2 m (HR 1.20) |
| KEYNOTE-181 Kojima et al.36 | 3 | Advanced OAC (n = 227) or OSCC (n = 401) | 2nd line | Pembrolizumab vs TPC | – | – | ITT: 7.1 m vs 7.1 m SCC: 8.2 m vs 7.1 m CPS > 10: 9.3 m vs 6.7 m |
| 1st line | |||||||
| KEYNOTE-062 Tabernero et al.27 | 3 | GC/GOJ (PD-L1 CPS ≥ 1%) | 1st line | Pembrolizumab (P) (n = 256) pembrolizumab + chemotherapy (P + CTx) (n = 257) chemotherapy (CTx) (n = 250) | P v CTx: 14.8% vs 37.2% CPS ≥ 10: 25.0% vs 37.8% | P v CTx CPS ≥ 1: 2.0 m v 6.4 m (HR 1.66), CPS ≥ 10: 2.9 m v 6.1 m (HR 1.10) | P v CTx ITT: 12.5 m v 11.1 m (HR 0.85) CPS ≥ 1: 10.6 m v 11.1 m (HR 0.91) CPS ≥ 10: 17.4 m vs 10.8 m (HR 0.69) |
| ATTRACTION-4 Boku et al.39 | 2 | GC/GOJ (n = 724) | 1st line | Nivolumab (n = 362)+CTx (SOX/CapOX) vs CTx alone (n = 362) | 58% vs 48% | 10.5 vs 8.4 (HR 0.68) | 17.5 m vs 17.2 (HR 0.90) |
| KEYNOTE-590 Kato et al.41 | 3 | OAC or OSCC (n = 749) | 1st line | Chemotherapy + /pembrolizumab | OSCC: 45% vs 29.3% | – | OSCC (all): 12.6 m vs 9.8 m (HR 0.72) OSCC (CPS ≥ 10): 13.9 m vs 8.8 m (HR 0.57) ITT 12.4 m vs 9.8 m |
| CHECKMATE 649 Moehler et al.40 | 3 | GC/GOJ (n = 1266, including Ipilimumab/nivolumab arm) | 1st line | Nivolumab+chemotherapy (n = 473) chemotherapy alone (n = 482) | CPS > 5: 60% vs 45% | CPS ≥ 5: 7.7 m vs 6.0 m (HR 0.68) | CPS ≥ 5: 14.4 m vs 11.1 m (HR 0.71, P < 0.0001) |
| ICI maintenance | |||||||
| JAVELIN 100 Moehler et al.4 | 3 | GC/GOJ (n = 805, of whom 499 entered 2nd phase) | 1st line maintenance | Avelumab (n = 249) vs ongoing chemotherapy (n = 250) | 13.3% vs 14.4% 1-year duration of response 62.3% vs 28.4% | HR 1.04 (0.85–1.28) | 10.4 m vs 10.9 m (HR 0.91, P = 0.1779) 24–month OS 22.1% vs 15.5% |
DCR disease control rate, PFS progression-free survival, OS overall survival, HR hazard ratio, NS non-significant, m month, SOX S-1/oxaliplatin, CapOx capecitabine/oxaliplatin, GOJ gastroesophageal junctional, GC gastric cancer, OAC oesophageal adenocarcinoma, OSCC oesophageal squamous cell carcinoma, PD-L1 programmed death ligand 1, TPC treatment of physicians choice, CPS combined positivity score.