TABLE 1

Immunotherapy trials in small cell lung cancer

Study [ref.]Trial designMedicationNumber of patientsPFS (months)OS (months)
Adjuvant in limited disease
 STIMULI [31]Phase 2, open-label1) Nivolumab+ipilimumab
2) Observation
153, closed early10.7Was not met
 ADRIATIC [32]Phase 3, RCT, double-blind1) Durvalumab+placebo
2) Durvalumab+tremelimumab
3) Placebo+placebo
600, recruiting
First-line in metastasised SCLC
NCT01331525 [33]Phase 2, RCT, double-blind1) Carboplatin/etoposide+ipilimumab426.917.0
2) Carboplatin/etoposide+placebo1 year PFS: 15.8% (6/35 patients)
NCT00527735 [34]Phase 2, RCT, double-blind1) Carboplatin/paclitaxel+placebo (control arm)1305.212.9
2) Carboplatin/paclitaxel+ipilimumab followed by paclitaxel+carboplatin+placebo (concurrent arm)3.99.1
3) Carboplatin/paclitaxel+placebo followed by carboplatin/paclitaxel+ipilimumab (phased arm)5.29.9
 IDEATE [35]Phase 3, RCT, double-blind1) Cisplatin/etoposide+ipilimumab11324.611.0
2) Cisplatin/etoposide+placebo4.410.9
 IMpower133 [36, 37]Phase 3, RCT, double-blind1) Carboplatin/etoposide+atezolizumab4035.212.3
2) Carboplatin/etoposide+placebo4.310.3
HR PFS 0.78HR OS 0.73
 CASPIAN [39, 40]Phase 3, RCT, open-label1) Platinum/etoposide+durvalumab+tremelimumab2684.910.4
HR PFS 0.84HR OS 0.82
2) Platinum/etoposide+durvalumab2685.112.9
HR PFS 0.78HR OS 0.73
3) Platinum/etoposide26910.5
 KEYNOTE-604 [42]Phase 3, RCT, double-blind1) Platinum/etoposide+pembrolizumab4534.510.8
2) Platinum/etoposide+placebo4.39.7
HR PFS 0.75HR OS 0.80
 ECOG-ACRIN EA5161 [45]Phase 2, RCT, double-blind1) Platinum/etoposide+nivolumab1605.511.3
2) Platinum/etoposide4.611.3
HR PFS 0.68HR OS 0.67
 REACTION [46]Phase 2, RCT,1) Platinum/etoposide+pembrolizumab5.412.3
2) Platinum/etoposide+placebo4.710.4
HR PFS 0.84HR OS 0.73
Maintenance after first-line chemotherapy
NCT02359019 [47]Phase 2, single armPembrolizumab451.4 irPFS 4.79.2
 Checkmate 451 [48]Phase 3, RCT, double-blind1) Nivolumab280HR PFS 0.67HR OS 0.84
2) Nivolumab+ipilimumab279HR PFS 0.72HR OS 0.92
3) Placebo275
 RAPTOR [49]Phase 2–3, RCT1) Atezolizumab after response on chemotherapy and atezolizumab138 phase 2Primary end-point PFS in phase 2
2) Atezolizumab+(extra-)thoracic radiotherapy after response on chemotherapy and atezolizumab186 phase 3Primary end-point OS in phase 3
Progression after first-line chemotherapy
 Checkmate 331 [50]Phase 3, RCT1) Nivolumab5697.5
2) Topotecan8.4
 Checkmate 032 [51]Phase 1/2, open-labelNivolumab±ipilimumab in different dosages216
1) Nivolumab 3 mg·kg−11) ORR 10%
2) Nivolumab 1 mg·kg−1+ipilimumab 3 mg·kg−12) ORR 23%
3) Nivolumab 3 mg·kg−1+ipilimumab 1 mg·kg−13) ORR 19%
 Checkmate 032 [52]Phase 1/2, open-labelNivolumab monotherapy 3 mg·kg−1 beyond third lineORR 11.9%
 KEYNOTE-028 [54]Phase 1b, single armPembrolizumab249.7
ORR 33%
 KEYNOTE-158 [55]Phase 2, single armPembrolizumab1072.09.0 (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, 2:11) Atezolizumab491.49.5
2) Conventional chemotherapy244.38.7
 BALTIC [57]Phase 2, open-labelDurvalumab+tremelimumab21ORR 9.5%
 MISP-MK3475 [58]Phase 2, single-arm, open-labelPaclitaxel+pembrolizumab265.09.1
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.