Table 1.
Randomized phase II and III clinical trials with reported results in resectable NSCLC.
| Name/NCT identifier | Phase | No. of patients | Population | Treatment | Primary endpoint(s) | Primary or key result(s) |
|---|---|---|---|---|---|---|
| Adjuvant immunotherapy (with CT or optional CT) | ||||||
| CANOPY-A NCT03447769 |
III | 1382 | Stage II-IIIB | Canakinumab vs placebo (optional adjuvant CT) | DFS | HR 0.94 (95% CI 0.78–1.14) |
| IMpower010 NCT02486718 |
III | 1280 | Stage IB-IIIA–II: 47%–IIIA: 41% | Sequential CT + atezolizumab vs sequential CT + BSC | DFS | Stage II-IIIA PD-L1 ≥1%: HR 0.66 (95% CI 0.50–0.88) Stage II-IIIA: HR 0.79 (95% CI 0.64–0.96) Stage IB-IIIA: HR 0.81 (95% CI 0.67–0.99) |
| PEARLS/KEYNOTE-091 NCT02504372 |
III | 1177 | Stage IB-IIIA–II: 57%–IIIA: 29% | Pembrolizumab vs placebo (optional adjuvant CT) | DFS | Stage IB-IIIA: HR 0.76 (95% CI 0.63–0.91) PD-L1 ≥50%: HR 0.82 (95% CI 0.57–1.18) |
| Neoadjuvant immunotherapy (with or without CT) | ||||||
| CANOPY-N NCT03968419 |
II | 88 | Stage IB-IIIA | Canakinumab, pembrolizumab, or combined | MPR | Canakinumab: MPR 2.9% Pembrolizumab: MPR 11.1% Combined: MPR 17.1% |
| NeoCOAST NCT03794544 |
II | 84 | Stage I-IIIA | Durvalumab, durvalumab + oleclumab, durvalumab + monalizumab, or durvalumab + danvatirsen | MPR | Durvalumab: MPR 11.1% Oleclumab: MPR 19.0% Monalizumab: MPR 30.0% Danvatirsen: MPR 31.3% |
| NEOSTAR NCT03158129 |
II | 44 | Stage I-IIIA | Nivolumab vs nivolumab + ipilimumab | MPR | Nivolumab: MPR 22% (5/23) Nivolumab + ipilimumab: MPR 38% (8/21) |
| TD-FOREKNOW NCT04338620 |
II | 88 | Stage IIIA-IIIB | CT + camrelizumab vs CT | pCR | Camrelizumab: pCR 32.6% (14/43) CT: pCR 8.9% (4/45) |
| CheckMate 816 NCT02998528 |
III | 358 | Stage IB-IIIA–IB/II: 36%–IIIA: 64% | CT + nivolumab vs CT | EFS, pCR | HR 0.68 (95% CI 0.49–0.93) Nivolumab: pCR 24.0% (43/179), MPR 36.9% CT: pCR 2.2% (4/179), MPR 8.9% |
| Neoadjuvant immunotherapy (with CT) followed by surgery and adjuvant immunotherapy (with or without CT) | ||||||
| NADIM II NCT03838159 |
II | 86 | Stage IIIA-IIIB | CT + nivolumab vs neoadjuvant CT alone | pCR | Nivolumab: pCR 37% (21/57) CT: pCR 7% (2/29) |
| neoSCORE NCT04459611 |
II | 60 | Stage IB-IIIA | Neoadjuvant CT + sintilimab (2 cycles) then adjuvant CT (2 cycles) + sintilimab vs neoadjuvant CT + sintilimab (3 cycles) then adjuvant CT (1 cycle) + sintilimab | MPR | 2 cycles: MPR 26.9% (7/26) 3 cycles: MPR 41.4% (12/29) |
| AEGEAN NCT03800134 |
III | 740 | Stage II-IIIB–IIIA/B: 71% | CT + durvalumab vs CT + placebo | EFS, pCR | HR 0.68 (95% CI 0.53–0.88) Durvalumab: pCR 17.2% (63/366), MPR 33.3% Placebo: pCR 4.3% (16/374), MPR 12.3% |
| CheckMate 77T NCT04025879 |
III | 461 | Stage II-IIIB–IIIA/B: 64% | CT + nivolumab vs CT + placebo | EFS | HR 0.58 (97.36% CI 0.42–0.81) Nivolumab: pCR 25.3%, MPR 35.4% Placebo: pCR 4.7%, MPR 12.1% |
| KEYNOTE-671 NCT03425643 |
III | 797 | Stage II-IIIB–IIIA/B: 70% | CT + pembrolizumab vs CT + placebo | EFS, OS | OS: HR 0.72 (95% CI 0.56–0.93) EFS: HR 0.59 (95% CI 0.48–0.72) Pembrolizumab: pCR 18.1%, MPR 30.2% Placebo: pCR 4.0%, MPR 11.0% |
| Neotorch NCT04158440 |
III | 404a | Stage II-III | Neoadjuvant CT + toripalimab (3 cycles) then adjuvant CT (1 cycle) + toripalimab vs neoadjuvant CT + placebo (3 cycles) then adjuvant CT (1 cycle) + placebo | ÈFS, MPR | HR 0.40 (95% CI 0.28–0.57) Toripalimab: MPR 48.5% (98/202), pCR 24.8% Placebo: MPR 8.4% (17/202), pCR 1.0% |
| RATIONALE-315 NCT04379635 |
III | 453 | Stage II-IIIA–IIIA: 58% | CT + tislelizumab vs CT + placebo | ÈFS, MPR | Tislelizumab: MPR 56.2% (127/226), pCR 40.7% Placebo: MPR 15.0% (34/227), pCR 5.7% |
| Adjuvant targeted therapy (with or without CT) | ||||||
| CORIN NCT02264210 |
II | 128 | Stage IB, EGFRm | Icotinib vs observation | 3-year DFS | 3-year DFS: Icotinib 96.1% vs observation 84.0% HR: 0.23 (95% CI 0.07–0.81) |
| EVAN NCT01683175 |
II | 102 | Stage IIIA, EGFRm | Erlotinib vs CT | 2-year DFS | 2-year DFS: Erlotinib 81.4% vs CT 44.6% HR 0.27 (95% CI 0.14–0.53) |
| ICOMPARE NCT01929200 |
II | 109 | Stage II-IIIA, EGFRm | 2-year icotinib vs 1-year icotinib | DFS | HR 0.51 (95% CI 0.28–0.94) |
| IFCT-0703 NCT00775307 |
II/III | 142 | Stage I | Pazopanib vs placebo | Compliance | RFS: HR 1.3 (95% CI 0.6–2.7) OS: HR 1.8 (95% CI 0.6–5.5) |
| ADAURA NCT02511106 |
III | 682 | Stage IB-IIIA, EGFRm | Osimertinib vs placebo (optional adjuvant CT) | DFS | Stage II-IIIA: DFS HR 0.23 (95% CI 0.18–0.30), OS HR 0.49 (95.03% CI 0.33–0.73) Stage IB-IIIA: DFS HR 0.27 (95% CI 0.21–0.34), OS HR 0.49 (95.03% CI 0.34–0.70) |
| ALINA NCT03456076 |
III | 257 | Stage IB-IIIA, ALK+ | Alectinib vs CT | DFS | Stage II-IIIA: HR 0.24 (95% CI 0.13–0.45) Stage IB-IIIA: HR 0.24 (95% CI 0.13–0.43) |
| BR19 NCT00049543 |
III | 503 | Stage IB-IIIA | Gefitinib vs placebo (optional adjuvant CT) | OS | HR 1.24 (95% CI 0.94–1.64) |
| CTONG1104 NCT01405079 |
III | 222 | Stage II-IIIA, EGFRm | Gefitinib vs CT | DFS | HR 0.56 (95% CI 0.40–0.79) |
| ECOG-E1505 NCT00324805 |
III | 1501 | Stage IB-IIIA | CT + bevacizumab vs CT | OS | HR 0.99 (95% CI 0.82–1.19) |
| EVIDENCE NCT02448797 |
III | 322 | Stage II-IIIA, EGFRm | Icotinib vs CT | DFS | HR 0.36 (95% CI 0.24–0.55) |
| IMPACT UMIN000006252 |
III | 234 | Stage II-IIIB, EGFRm | Gefitinib vs CT | DFS | HR 0.92 (95% CI 0.67–1.28) |
| RADIANT NCT00373425 |
III | 1252 | Stage IB-IIIA, EGFRm | Erlotinib vs placebo (optional adjuvant CT) | DFS | HR 0.90 (95% CI 0.74–1.10) |
| Neoadjuvant targeted therapy | ||||||
| CTONG1103 NCT01407822 | II | 72 | Stage IIIA, EGFRm | Erlotinib (both neoadjuvant and adjuvant) vs CT (both neoadjuvant and adjuvant) | ORR | Erlotinib: 54.1% CT: 34.3% |
Abbreviations: NSCLC, non-small cell lung cancer; NCT, national clinical trial; CT, chemotherapy; DFS, disease-free survival; HR, hazard ratio; CI, confidence interval; BSC, best supportive care; PD-L1, programmed cell death ligand 1; MPR, major pathological response; pCR, pathological complete response; EFS, event-free survival; OS, overall survival; EGFRm, activating epidermal growth factor receptor mutation; RFS, recurrence-free survival; ALK+, anaplastic lymphoma kinase alteration; UMIN, university hospital medical information network; ORR, objective response rate.
a
Based on the stage III interim analysis.