Table 1.
Summary of trials in first-line and/or maintenance setting for extensive stage small-cell lung cancer
| Trial ID | Phase | N | Study design | Treatment | Endpoint | PFS | OS |
|---|---|---|---|---|---|---|---|
| First-line trials | |||||||
| NCT00527735 | II | 130 | Randomised, double-blind to assess Ipi in combination plus ChT | Arm A (concurrent ): Ipi + ChT × 4C → ChT × 2C Arm B (phased): ChT × 2C → Ipi + ChT × 4C Control arm: ChT + placebo × 4-6C |
irPFS | 5.7, 6.4, 5.3 moa (A, B, control) HR 0.93; P = 0.37 (A versus control) HR 0.64; P = 0.03 (B versus control) |
9.1, 12.9, 9.9 mo (A, B, control) HR 0.95, P = 0.41 (A versus control) HR 0.76, P = 0.13 (B versus control) |
| NCT01331525 (ICE) | II | 42 | Open-label, single-arm to evaluate Ipi in combination plus PE | Arm A: PE (up to 6C) + Ipi | 1-year PFS | 6.9 mo 1 year-PFS 15.8% |
17.0 mo |
| NCT01450761 | III | 1132 | Randomised, double-blind of phased Ipi plus PE | Arm A: PE × 4C + phased Ipi × 4C Control arm: PE × 4C + phased placebo × 4C |
OS | 4.6 versus 4.4 mo HR 0.85, P = 0.0161 |
11 versus 10.9 mo HR 0.94, P = 0.3775 |
| NCT02763579 (IMpower133) | III | 403 | Randomised trial, double-blind of PE + atezolizumab or placebo | Arm A: PE + atezolizumab × 4C → atezolizumab Control arm: PE + placebo × 4C → placebo |
PFS, OS | 5.2 versus 4.3 mo HR 0.77, P = 0.02 |
12.3 versus 10.3 mo HR 0.70, P = 0.007 |
| NCT03043872 (CASPIAN) | III | 805 | Randomised trial, open-label of PE with/out durvalumab and tremelimumab |
Arm A: durvalumab + tremelimumab + EP × 4C → durvalumab + tremelimumab Arm B: durvalumab + EP × 4C → durvalumab Control arm: EP for up to 4C |
OS | 5.1 versus 5.4 mo (B versus control) HR 0.78; P not tested 4.9 versus 5.4 mo (A versus control) HR, 084 P not tested |
12.9 versus 10.5 mo (B versus control) HR 0.75, P = 0.0032 10.5 versus 10.4 mo (A versus control) HR 0.82, P = 0.0451 |
| NCT03066778 (KEYNOTE-604) | III | 453 | Randomised, double-blind, placebo-controlled of PE with/out pembrolizumab | Arm A: pembrolizumab + PE Control arm: PE + placebo |
PFS, OS | 4.5 versus 4.3 mo HR 0.75, P = 0.0023 |
10.8 versus 9.7 mo HR, 0.80; P = 0.0164b |
| NCT03382561 (ECOG-ACRIN EA5161) | II | 160 | Randomised, open-label of PE with/out nivolumab | Arm A: PE + nivolumab × 4C → nivolumab Control arm: PE |
PFS | 5.5 versus 4.7 mo HR 0.68 P = 0.0047 |
11.3 versus 8.5 mo HR 0.67 P = 0.038 |
| Maintenance trials | |||||||
| NCT02359019 | II | 45 | Open-label, single-arm study of pembrolizumab maintenance in patients not progressing to PE | Arm A: pembrolizumab × 2 years | PFS | 1.4 mo | 9.0 mo |
| NCT02538666 (Check-Mate 451) | III | 834 | Double-blind study of nivolumab + Ipi versus nivolumab versus placebo as maintenance in patients not progressing to PE | Arm A: nivolumab + Ipi × 4C → nivolumab × 2 years Arm B: nivolumab × 2 years Control arm: placebo × 2 years |
OS | 1.7 versus 1.4 mo (A versus control) HR 0.72 1.9 versus 1.4 mo (B versus control) HR 0.67 |
9.2 versus 9.6 mo (A versus placebo) HR 0.92; P = 0.3893 10.4 versus 9.6 mo (B versus control) HR 0.84 (P not tested) |
C, cycles; ChT, chemotherapy; HR, hazard ratio; Ipi, ipilimumab; irPFS, immune-related progression-free survival; mo, months; OS, overall survival; PE, platinum and etoposide; PFS, progression-free survival.
a
irPFS.
b
Superiority threshold P = 0.0128.