Study [ref.] | Trial design | Medication | Number of patients | PFS (months) | OS (months) |
Adjuvant in limited disease | |||||
STIMULI [31] | Phase 2, open-label | 1) Nivolumab+ipilimumab 2) Observation | 153, closed early | 10.7 | Was not met |
ADRIATIC [32] | Phase 3, RCT, double-blind | 1) Durvalumab+placebo 2) Durvalumab+tremelimumab 3) Placebo+placebo | 600, recruiting | ||
First-line in metastasised SCLC | |||||
NCT01331525 [33] | Phase 2, RCT, double-blind | 1) Carboplatin/etoposide+ipilimumab | 42 | 6.9 | 17.0 |
2) Carboplatin/etoposide+placebo | 1 year PFS: 15.8% (6/35 patients) | ||||
NCT00527735 [34] | Phase 2, RCT, double-blind | 1) Carboplatin/paclitaxel+placebo (control arm) | 130 | 5.2 | 12.9 |
2) Carboplatin/paclitaxel+ipilimumab followed by paclitaxel+carboplatin+placebo (concurrent arm) | 3.9 | 9.1 | |||
3) Carboplatin/paclitaxel+placebo followed by carboplatin/paclitaxel+ipilimumab (phased arm) | 5.2 | 9.9 | |||
IDEATE [35] | Phase 3, RCT, double-blind | 1) Cisplatin/etoposide+ipilimumab | 1132 | 4.6 | 11.0 |
2) Cisplatin/etoposide+placebo | 4.4 | 10.9 | |||
IMpower133 [36, 37] | Phase 3, RCT, double-blind | 1) Carboplatin/etoposide+atezolizumab | 403 | 5.2 | 12.3 |
2) Carboplatin/etoposide+placebo | 4.3 | 10.3 | |||
HR PFS 0.78 | HR OS 0.73 | ||||
CASPIAN [39, 40] | Phase 3, RCT, open-label | 1) Platinum/etoposide+durvalumab+tremelimumab | 268 | 4.9 | 10.4 |
HR PFS 0.84 | HR OS 0.82 | ||||
2) Platinum/etoposide+durvalumab | 268 | 5.1 | 12.9 | ||
HR PFS 0.78 | HR OS 0.73 | ||||
3) Platinum/etoposide | 269 | 10.5 | |||
KEYNOTE-604 [42] | Phase 3, RCT, double-blind | 1) Platinum/etoposide+pembrolizumab | 453 | 4.5 | 10.8 |
2) Platinum/etoposide+placebo | 4.3 | 9.7 | |||
HR PFS 0.75 | HR OS 0.80 | ||||
ECOG-ACRIN EA5161 [45] | Phase 2, RCT, double-blind | 1) Platinum/etoposide+nivolumab | 160 | 5.5 | 11.3 |
2) Platinum/etoposide | 4.6 | 11.3 | |||
HR PFS 0.68 | HR OS 0.67 | ||||
REACTION [46] | Phase 2, RCT, | 1) Platinum/etoposide+pembrolizumab | 5.4 | 12.3 | |
2) Platinum/etoposide+placebo | 4.7 | 10.4 | |||
HR PFS 0.84 | HR OS 0.73 | ||||
Maintenance after first-line chemotherapy | |||||
NCT02359019 [47] | Phase 2, single arm | Pembrolizumab | 45 | 1.4 irPFS 4.7 | 9.2 |
Checkmate 451 [48] | Phase 3, RCT, double-blind | 1) Nivolumab | 280 | HR PFS 0.67 | HR OS 0.84 |
2) Nivolumab+ipilimumab | 279 | HR PFS 0.72 | HR OS 0.92 | ||
3) Placebo | 275 | ||||
RAPTOR [49] | Phase 2–3, RCT | 1) Atezolizumab after response on chemotherapy and atezolizumab | 138 phase 2 | Primary end-point PFS in phase 2 | |
2) Atezolizumab+(extra-)thoracic radiotherapy after response on chemotherapy and atezolizumab | 186 phase 3 | Primary end-point OS in phase 3 | |||
Progression after first-line chemotherapy | |||||
Checkmate 331 [50] | Phase 3, RCT | 1) Nivolumab | 569 | 7.5 | |
2) Topotecan | 8.4 | ||||
Checkmate 032 [51] | Phase 1/2, open-label | Nivolumab±ipilimumab in different dosages | 216 | ||
1) Nivolumab 3 mg·kg−1 | 1) ORR 10% | ||||
2) Nivolumab 1 mg·kg−1+ipilimumab 3 mg·kg−1 | 2) ORR 23% | ||||
3) Nivolumab 3 mg·kg−1+ipilimumab 1 mg·kg−1 | 3) ORR 19% | ||||
Checkmate 032 [52] | Phase 1/2, open-label | Nivolumab monotherapy 3 mg·kg−1 beyond third line | ORR 11.9% | ||
KEYNOTE-028 [54] | Phase 1b, single arm | Pembrolizumab | 24 | 9.7 | |
ORR 33% | |||||
KEYNOTE-158 [55] | Phase 2, single arm | Pembrolizumab | 107 | 2.0 | 9.0 (PDL-1+ 14.6 months and in PDL-1− 7.7 months) ORR 18.7%, ORR in PDL-1+ 35.7% and in PDL-1− 6.0% |
IFCT-1603 [56] | Phase 2, randomised, 2:1 | 1) Atezolizumab | 49 | 1.4 | 9.5 |
2) Conventional chemotherapy | 24 | 4.3 | 8.7 | ||
BALTIC [57] | Phase 2, open-label | Durvalumab+tremelimumab | 21 | ORR 9.5% | |
MISP-MK3475 [58] | Phase 2, single-arm, open-label | Paclitaxel+pembrolizumab | 26 | 5.0 | 9.1 |
ORR 23.1% |
PFS: progression free survival; OS: overall survival; RCT: randomised controlled trial; SCLC: small cell lung cancer; HR: hazard ratio; irPFS: immune-related progression free survival; ORR: overall response rate; PDL-1: programmed death ligand-1.