Table 3.
Randomized trials assessing first-line immunotherapy in stage IV NSCLC.
| References | Histology | Treatment | N pts | RR | p | mPFS | p | MST | p |
|---|---|---|---|---|---|---|---|---|---|
| Immunotherapy monotherapy vs. chemotherapy | |||||||||
| Carbone et al. (37) | NSCLC (PD-L1 ≥ 1%) | Nivolumab | 211 | 26% | NS | 4.2 m | 0.25 | 14.4 m | NS |
| Platinum doublet | 212 | 33% | 5.9 m | 13.2 m | |||||
| Reck et al. (38) | NSCLC (PD-L1>50%) | Pembrolizumab | 154 | 44.8% | – | 10.3 m | <0.001 | HR 0.60 (IC 95% 0.41–0.89) |
0.005 |
| Platinum doublet | 151 | 27.8% | 6.0 m | ||||||
| Mok et al. (39) | NSCLC (PD-L1 ≥ 1%) | Pembrolizumab | 637 | 27% | – | 5.4 m | NS | 16.7 m | 0.0018 |
| Platinum doublet | 637 | 27% | 6.5 m | 12.1 m | |||||
| Hellmann et al. (40) | NSCLC (PD-L1 ≥ 1% + high TMB) | Nivolumab + ipilimumab | 139 | 45.3% | – | 7.2 m | <0.001 | – | – |
| CDDP/CBDCA-PEM or GEM | 160 | 26.9% | 5.5 m | – | |||||
| Hellmann et al. (41) | NSCLC (PD-L1 ≥ 1%) | Nivolumab + ipilimumab | 396 | 35.9% | – | – | – | 17.1 m | 0.007 |
| CDDP/CBDCA-PEM or GEM | 397 | 30% | – | 14.9 m | |||||
| Rizvi et al. (42) | PDL1>25% | Durvalumab | 163 | 4.7 m | 16.3 m | 0.036 | |||
| Durvalumab + Tremelimumab | 163 | 3.9 m | 11.9 m | 0.202 | |||||
| Platinum-PEM or GEM or PTX | 162 | 5.4 m | 12.9 m | ||||||
| Antonia et al. (43, 44) | Stage III NSCLC$ | Durvalumab | 473 | 28.4% | <0.001 | 17.2 m | <0.001 | NR | |
| Placebo | 236 | 16% | 5.6 m | 28.7 m | 0.0025 | ||||
| Immuno-chemotherapy vs. chemotherapy | |||||||||
| Langer et al. (45)* | NSCLC | CBDCA-PEM-Pembrolizumab | 60 | 55% | 0.0016 | 13.0 m | 0.01 | HR 0.90 (IC 95% 0.42–1.91) |
NS |
| CBDCA-PEM | 63 | 26% | 8.9 m | ||||||
| Paz-Ares et al. (46) | Squamous | CBDCA-(nab)PTX-Pembrolizumab | 278 | 57.9% | – | 6.4 m | <0.001 | 15.9 m | <0.001 |
| CBDCA-(nab)PTX | 281 | 38.4% | 4.8 m | 11.3 m | |||||
| Gandhi et al. (47) | Non-squamous | CDDP/CBDCA-PEM-Pembrolizumab | 410 | 47.6% | <0.001 | 8.8 m | <0.001 | NR | <0.001 |
| CBDCA-PEM | 206 | 18.9% | 4.9 m | 11.3 m | |||||
| Socinski et al. (48) | Non-squamous | CBDCA-PTX-Beva-Atezolizumab | 400 | 63.5% | – | 8.3 m | <0.001 | 19.2 m | 0.02 |
| CBDCA-PTX-Beva | 400 | 48% | 6.8 m | 14.7 m | |||||
| Lynch et al. (49)* | NSCLC | CBDCA-PTX | 66 | 14% | – | 4.6 m | 8.3 m | ||
| CBDCA-PTX-concurrent ipilimumab | 70 | 21% | 5.5 m | 0.13 | 9.7 m | 0.48 | |||
| CBDCA-PTX-phased ipilimumab | 68 | 32% | 5.7 m | 0.05 | 12.2 m | 0.23 | |||
| Papadimitrakopoulou (50) | Non squamous | CBDCA/CDDP-PEM-Atezolizumab | 292 | 7.6 m | <0.0001 | 18.1 m | 0.08 | ||
| CBDCA/CDDP-PEM | 286 | 5.2 m | 13.6 m | ||||||
| Cappuzzo et al. (51) | Non-squamous | CBDCA-nabPTX-Atezolizumab | 451 | 49.2% | – | 7.0 m | <0.0001 | 18.6 m | 0.033 |
| CBDCA-nabPTX | 228 | 31.9% | 5.5 m | 13.9 m | |||||
| Jotte et al. (52) | Squamous | CBDCA-nabPTX-Atezolizumab | 343 | 6.3 m | 0.0001 | 14.0 m | 0.69 | ||
| CBDCA-nabPTX | 340 | 5.6 m | 13.9 m | ||||||
| Govindan et al. (53) | Squamous | CBDCA-PTX-ipilimumab | 388 | 44% | – | 5.6 m | 0.07 | 13.4 m | 0.25 |
| CBDCA-PTX | 361 | 47% | 5.6 m | 12.4 m | |||||
RR, response rate; mPFS, median progression free survival; MST, median survival time; NSCLC, non-small cell lung cancer; m, months; NS, not significant; CBDCA, carboplatin; PEM, pemetrexed; HR, hazard ratio; CI, confidence interval; PTX, paclitaxel; CDDP, cisplatin; NR, not reached; TMB, tumor mutation burden; GEM, gemcitabine; Beva, bevacizumab.
*
Randomized phase II.
$
Non-progressing stage III NSCLC after concomitant chemoradiotherapy.