Table 1.
First-line ICI Clinical Trials in EGFRm NSCLC.
| Trial | Phase | Intervention | Outcome | Safety | Reference | |
|---|---|---|---|---|---|---|
| ICI Monotherapy | ||||||
| CheckMate 012 | 1 | Nivolumab | ORR: 14% for EGFRm vs 30% for EGFRwt PFS: 1.8 vs 6.6 mo |
G3-4#: 17%, G5: 0% | (37) | |
| NCT02879994 | 2 | Pembrolizumab | ORR: 0%* | TRAE: 46%, no G4-5 6/7 patients had a TRAE on second-line EGFR TKI, including one G5 pneumonitis |
(38) | |
| ICI + Chemotherapy | ||||||
| CheckMate 012 | 1 | Nivolumab + PT-DC | ORR: 17% for EGFRm vs 47% for EGFRwt PFS: 4.8 vs 7.5 mo OS: 20.5 vs 24.5 mo |
G3-4#: 50%, G5: 0%. Pneumonitis most common TRAE (7%) | (39) | |
| ICI + EGFR TKI Therapy | ||||||
| NCT02088112 | 1 | Gefitinib + durvalumab dose escalation | ORR: 63.3%-70% PFS: 10.1-12.0 mo |
TRAE: 100%, 17/40 high-grade hepatic AEs | (40) | |
| KEYNOTE-021 | 3 | Pembrolizumab (P) + erlotinib (E) or gefitinib (G) | ORR: 41.7% P+E, 14.3% P + G PFS: 19.5 mo P+E, 1.4 mo P + G |
P+E: TRAE: 100%, G3: 33.3%, no G4-5 P+G: TRAE: 85.7%, G3-4: 71.4% hepatotoxic AEs |
(41) | |
| NCT02013219 | 1b | Atezolizumab + erlotinib | ORR: 75% PFS: 11.3 mo |
G3-4#: 39% | (42) | |
| Dual ICI Therapy | ||||||
| CheckMate 012 | 1 | Nivolumab + ipilimumab | ORR: 50% | TRAE#: 72-82%, G3-4: 33-37%, no G5 | (43) | |
Indicated categories of trials with respective trial parameters are given. *1/11 patients initially reported to respond but was found to be EGFRwt. ORR, overall response rate; PFS, progression-free survival; OS, overall survival; TRAE, Treatment related adverse event; G, grade of toxicity; PT-DC, platinum-doublet chemotherapy; #TRAEs for entire study population and not selected for EGFRm patients.