TABLE 1.
Pivotal registrational trials of ICB in the metastatic setting: melanoma & NSCLC.
| Regimen update doses and schedules | Number patients | Baseline characteristics | Objective response rate | Overall survival | ||
|---|---|---|---|---|---|---|
| Ipilimumab | 1st line | (Ipilimumab 10 mg/kg + dacarbazine) vs dacarbazine | 502 | Unresectable stage III or stage IV treatment naïve BRAF not assessed | 33.2 vs 30.2%, P = .41 | 11.2 vs 9.1 months, HR 0.72, P < .001 |
| 2nd line | Ipilimumab 3 mg/kg vs glycoprotein 100 | 676 | Unresectable stage III or stage IV, disease progressed post dacarbazine/temozolomide/foemustine/carboplatin/interleukin‐2 BRAF not assessed | 10.9% vs 1.5%, P = .001 | 10 vs 6.4 months, HR 0.68, P < .001 | |
| Nivolumab | 1st line | Nivolumab 3 mg/kg Q2W vs dacarbazine CHECKMATE 066 | 418 | Unresectable stage III or stage IV treatment naïve without a BRAF mutation | 40 vs 13.9%, P < .001 | 37.5 vs 11.2 months, HR 0.46, P < .01 |
| 2nd line | Nivolumab 3 mg/kg Q2W vs (dacarbazine or carboplatin + paclitaxel) CHECKMATE‐037 | 370 | Unresectable stage III or stage IV, disease progressed post ipilimumab and if BRAFv600 mutation positive a BRAF inhibitor | 31.7 vs 10.6%, P‐value not provided | 15.7 vs 14.4 months, HR 0.95, P = 0.716a | |
| Pembrolizumab | 1st line | (Pembrolizumab 10 mg/kg Q2W or Q3W) vs ipilimumab 3 mg/kg Q3W (4 doses) KEYNOTE‐006 | 834 | Unresectable stage III or stage IV, ≤1 systemic therapy and if BRAFv600 mutation positive a BRAF inhibitor not necessary if normal LDH and no rapidly progressive disease | Q2W (33.7 vs 11.9% P < .001 vs ipilimumab) and Q3W (32.9 vs 11.9% P < .001 vs ipilimumab | 32.7 vs 15.9 months, HR 0.73, P = .00049 |
| 2nd line | Pembrolizumab 2 mg/kg Q3W vs 10 mg/kg Q3W KEYNOTE‐001 | 173 | Unresectable stage III or stage IV, disease progressed post ipilimumab and if BRAFv600 mutation positive a BRAF inhibitor | 26% at 2 mg/kg and 10 mg/kg dose | 23.8 months (naïve and pretreated) | |
| Ipilimumab & Nivolumab | 1st line | Nivolumab 3 mg/kg Q2W vs Nivolumab 1 mg/kg Q3W + Ipilimumab 3 mg/kg Q3w (4 doses) followed by Nivolumab 3 mg/kg Q2W vs Ipilimumab 3 mg/kg Q3W (4 doses) | 945 | Unresectable stage III or stage IV, treatment naïve across BRAF mutant and wild‐type | 57.6% doublet vs 43.7% with single agent nivolumab vs 19% with single agent ipilimumab, P < .001 for both nivolumab containing arms over ipilimumab | Doublet NR vs 19.9 months HR 0.54, P < .0001 vs ipilimumab monotherapy). Doublet vs nivolumab monotherapy (NR vs 36.9 months HR descriptive 0.84 [0.67–1.05]) |
| Nivolumab | 2nd line | Nivolumab 3 mg/kg Q2W vs doctaxel CHECKMATE‐017 | 272 | Stage IV refractory squamous NSCLC | 20 vs 9%, P = .008 | 9.2 vs 6 months, HR:0.59, P < .001 |
| Nivolumab | 2nd line | Nivolumab 3 mg/kg Q2W vs doctaxel CHECKMATE‐057 | 582 | Stage IV refractory nonsquamous NSCLC | 19 vs 12%, P = .02 | 12.2 vs 9.4 months HR 0.73, P = .002 |
| Pembrolizumab | 1st line | Pembrolizumab 200 mg Q3W vs ICC of platinum doublet KEYNOTE‐024 | 305 | Stage IV refractory nonsquamous NSCLC without driver mutation ≥50% PD‐L1TPS | 44.8 vs 27.8%, P value not provided | 30 vs 14.2 months with chemotherapy HR 0.63, P = .002 |
| 2nd line | Pembrolizumab 2 mg/kg Q3W vs Pembrolizumab 10 mg/kg Q3W vs docetaxel KEYNOTE‐010 | 1034 | Stage IV refractory NSCLC PD‐L1 expression ≥1% | 18% at 2 mg/kg vs 18% at 10 mg/kg vs 9% docetaxel, P = .005 for 2 mg/kg and P = .0002 for 10 mg/kg | 10.4 vs 8.5 months for pembrolizumab 2 mg/kg HR 0.71, P < .0008), 12.7 vs 8.5 months for pembrolizumab 10 mg/kg, HR 0.61, P < .0001 | |
| Atezolizumab | 2nd line | Atezolizumab 1200 mg Q3W vs docetaxel OAK trial | 1225 | Stage IV refractory NSCLC | 14 vs 13%, P value not provided | Median overall survival 13.8 vs 9.6 months, HR 0.73, P = .0003 |
| Pembrolizumab & Pemetrexed & carboplatin/cisplatin | 1st line | [Pembrolizumab 200 mg Q3W + pemetrexed + cisplatin/carboplatin] vs [placebo + pemetrexed + cisplatin/carboplatin] KEYNOTE‐189 | 616 | Stage IV refractory nonsquamous NSCLC without driver mutation | 47.6 vs 18.9%, P < .001 | 22 vs 10.7 months, HR .56, P < .00001 |
| Atezolizumab & Bevacizumab & carboplatin & paclitaxel | 1st line | [Atezolizumab 1200 mg Q3W + bevacizumab + paclitaxel + carboplatin vs [bevacizumab + carboplatin] vs [atezolizumab 1200 mg Q3W + paclitaxel + carboplatin] IMpower150 | 1202 | Stage IV refractory nonsquamous NSCLC or post‐EGFR/ALK progression with targeted therapy | 63.5 vs 48%, P value not provided (ABCP vs BCP) | 19.2 vs 14.7 months, HR 0.78, P = .002 (ABCP vs BCP) |
a
Median overall survival similar due to dropout, crossover and imbalance in baseline characteristics.