Table 1. Approved combination of ICI (September 2019).
| Trial | Regimen | Disease and setting | Results |
|---|---|---|---|
| KEYNOTE-189 Gandhi et al [45]. Gadgeel et al [139]. |
Pembrolizumab plus pemetrexed and platinum CT | Metastatic non-squamous NSCLC, with no EGFR and anaplastic lymphoma kinase (ALK) genomic alterationsa First-line treatment |
mPFS 8.8 versus 4.9 months (HR 0.52; 95% CI, 0.43–0.64) mOS 22 versus 10.7 months (HR 0.56; 95% CI 0.45–0.70) |
| KEYNOTE-407 Paz-Ares et al [46]. |
Pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel | Metastatic squamous NSCLCa First-line treatment |
mOS 15.9 versus 11.3 months (HR 0.64; 95% CI, 0.49–0.85) |
| IMpower150 Socinski et al [47]. |
Atezolizumab plus bevacizumab, paclitaxel and carboplatin (versus bevacizumab plus paclitaxel plus carboplatin) |
Metastatic non-squamous NSCLC, with no EGFR and ALK genomic alterationsa First-line treatment |
mOS 19.2 versus 14.7 months (HR 0.78; 95% CI, 0.64–0.96) |
| IMpower130 West et al [48] |
Atezolizumab plus paclitaxel and carboplatin (versus paclitaxel plus carboplatin) |
Metastatic non-squamous NSCLC, with no EGFR and ALK genomic alterationsc First-line treatment |
mOS 18.6 versus 13.9 months (HR 0.79; 95% CI 0.64–0.98) |
| IMpower133 Horn et al [49] |
Atezolizumab plus carboplatin and etoposide (versus carboplatin plus etoposide) |
Extensive-stage SCLCa First-line treatment |
mOS 12.3 versus 10.3 months (HR 0.70; 95% CI 0.54–0.91) |
| KEYNOTE-048 Burtness et al [50] |
Pembrolizumab plus platinum and fluorouracil (versus platinum plus fluorouracil plus cetuximab) |
Metastatic or unresectable, recurrent HNSCCa First-line treatment |
mOS 13 versus 10.7 months (HR 0.77; 95% CI 0.63–0.93) |
| IMpassion130 Schmid et al [140] Schmid et al [141] |
Atezolizumab plus nab-paclitaxel (versus nab-paclitaxel) |
Metastatic or unresectable TNBC with PD-L1≥1%a First-line treatment |
mPFS ITT 7.2 versus 5.5 months (HR 0.8; 95% CI 0.69–0.92) mPFS PDL1+ 7.5 versus 5 months (HR 0.62; 95% CI, 0.49–0.78) mOS ITT 21 versus 18.7 months (HR 0.86, 95% CI 0.72–1.02) mOS PDL1+ 25 versus 18 months (HR 0.71, 95% CI 0.54–0.94) |
| CheckMate-067 Wolchok et al [142] Larkin et al [123] |
Nivolumab plus ipilimumab (versus nivolumab alone versus ipilimumab alone) |
Metastatic or unresectable melanomaa | mPFS 11.5 versus 6.9 versus 2.9 months (HR 0.43; 95% CI 0.35–0.52)d mOS NR versus 36.9 versus 19.9 months (HR 0.52; 95% CI 0.42–0.62)d |
| CheckMate-214 Motzer et al [124] |
Nivolumab plus ipilimumab (versus sunitinib) |
Advanced RCC at intermediate or poor riska First-line treatment |
mOS NR versus 26.6 months HR 0.66; 95% CI 0.54–0.80 mPFS 8.2 versus 8.3 months HR 0.77; 95% CI 0.65–0.90 ORR 42% versus 29% |
| CheckMate-142 Overman et al [125] |
Nivolumab plus ipilimumab (non randomized) |
MSI-H or dMMR metastatic CRC progressed on fluoropyrimidine, oxaliplatin and irinotecanb | ORR 55%, mDOR NR 12-months PFS 71% |
| KEYNOTE-426 Rini et al [120] |
Pembrolizumab plus axitinib (versus sunitinib) |
Advanced RCCa First-line treatment |
mPFS 15.1 versus 11.1 months HR 0.69; 95% CI 0.57–0.84 |
| JAVELIN Renal101 Motzer et al [119] |
Avelumab plus axitinib (versus sunitinib) |
Advanced RCCa First-line treatment |
mPFS 13.8 versus 8.4 months HR 0.69; 95% CI 0.56–0.84 |
a
Both FDA- and EMA-approved (for HNSCC combination strategy is approved in Europe only for PDL1+ patients)
b
Only FDA-approved, under accelerated approval procedure based on ORR and DOR data
c
Only EMA-approved
d
HR for nivo/ipi versus ipi
mOS: median Overall Survival