TABLE 1.
Clinical trials of immune checkpoint inhibitors in NSCLC patients with EGFR mutations
| Clinical trial | Phase | Treatment | Subgroup | Number | Outcome |
|---|---|---|---|---|---|
| Monotherapy | |||||
| KEYNOTE‐001 | II | Pembrolizumab | EGFR (+) | 10 | ORR = 0 |
| EGFR (+/−) | 495 | ORR = 19.4%; mDOR = 12.5 months; mOS = 12 months | |||
| CheckMate 012 | I | Nivolumab | EGFR (+) | 7 | ORR = 14%; mPFS = 1.8 months; DCR = 29% |
| EGFR (−) | 30 | ORR = 30%; mPFS = 6.6 months; DCR = 50% | |||
| KEYNOTE‐010 | III | Pembrolizumab | EGFR (+), PD‐L1 ≥1% | 86 |
OS: HR = 0.88, 95% CI = 0.45‐1.70); PFS: HR, 1.79 (0.94–3.42) |
| EGFR (−), PD‐L1 ≥1% | 875 |
OS: HR = 0.66, 95% CI = 0.55‐0.80; PFS: HR = 0.83, 95% CI = 0.71‐0.98 |
|||
| CheckMate 057 | III | Nivolumab vs. docetaxel | EGFR (+) | 44 |
ORR = 11%; OS: HR‐ = 1.18 (favors docetaxel) |
| EGFR (−) | 340 | OS: HR = 0.66 | |||
| OAK | III | Atezolizumab vs. docetaxel | EGFR (+), TKI‐pretreated | 85 |
ORR = 5%; OS: HR‐ = 1.24, 95% CI = 0.71‐2.18 |
| EGFR (−) | 628 | OS: HR = 0.69, 95% CI = 0.57‐0.83 | |||
| BIRCH | II | Atezolizumab | EGFR (+), PD‐L1 (TC2/3 or IC2/3, PD‐L1‐expressing cells) | 13 |
ORR = 31%; mOS = 26 months |
| EGFR (−) | 104 | ORR = 22%; mOS = 20.1 months | |||
| ATLANTIC | II | Durvalumab | EGFR+/ALK+, TKI‐pretreated, PD‐L1<25% | 30 | mPFS = 1.9 months; mOS = 9.9 months |
| EGFR‐/ALK‐, PD‐L1<25% | 94 | mPFS = 1.9 months; mOS = 9.3 months; | |||
| EGFR+, TKI‐pretreated, PD‐L1≥25% | 66 | mOS = 16.1 months | |||
| EGFR (−), PD‐L1≥25% | 149 | mOS = 10.9 months | |||
| Combined with EGFR‐TKIs | |||||
| KEYNOTE‐021 | II | Pembrolizumab + Erlotinib | EGFR (+), TKI‐pretreated | 12 | ORR = 41.7%; mOS = NR; mPFS = 19.5 months |
| Pembrolizumab + Gefitinib | 7 | ORR = 14.3%; mOS = 13 months; mPFS = 1.4 months | |||
| CheckMate 012 | I | Nivolumab + Elotinib | EGFR (+) | 21 | ORR = 19% |
| EGFR (+), TKI‐pretreated | 20 | ORR = 15%; mPFS = 16.6 months | |||
| TATTON | I | Durvalumab + Osimertinib | EGFR (+), TKI‐pretreated | 23 | ORR = 43% |
| EGFR (+), TKI‐naive | 11 | ORR = 70% | |||
| Double immunotherapy | |||||
| CheckMate 012 | I | Nivolumab + Ipilimumab | EGFR (+) | 8 | ORR = 50% |
| EGFR (−) | 54 | ORR = 41% | |||
| Combined with chemotherapy | |||||
| IMpower 130 | III | Atezolizumab + Chemotherapy vs. Chemotherapy | EGFR+/ALK+; TKI‐pretreated | NA |
OS: 14.4 vs. 10 months, HR = 0.98; PFS: 7.0 vs. 6.0 months, HR = 0.75 |
| EGFR‐/ALK‐ | 679 |
OS: 18.6 vs. 13.9 months, HR = 0.79; PFS: 7 vs. 5.5 months, HR = 0.64 |
|||
| CT18 | II | Toripalimab + Chemotherapy | TKI‐pretreated, without T790M | 40 |
ORR = 50%; DCR = 87.5%; mPFS = 7 months |
| Others | |||||
| IMpower 150 | III | ABCP | EGFR (+), TKI‐pretreated were included | 34 |
ORR = 71%; mPFS = 10.2 months; mOS = 26.1 months |
| ABCP | EGFR (−) | 359 | mOS = 19.5 months | ||
| ACP |
EGFR (+) TKI‐pretreated were included |
45 |
ORR = 36%; mPFS = 6.9 months; mOS = 21.4 months |
||
| ACP | EGFR (−) | 350 | mOS = 19.0 months; | ||
| BCP | EGFR (+), TKI‐pretreated were included | 44 | ORR = 42%; mPFS = 7.1 months; mOS = 20.3 months | ||
| BCP | EGFR (−) | 338 | mOS = 14.7 months | ||
| ABCP vs. BCP | TKI‐pretreated with sensitive EGFR mutation | 26 vs. 32 |
mOS, 29.4 vs. 18.1 months; HR = 0.60, 95% CI = 0.31‐1.34 |
||
Abbreviations: NSCLC, non‐small cell lung cancer; EGFR, epidermal growth factor receptor; ORR, overall response rate; mDOR, median duration of response; mOS, median overall survival; mPFS, median progression‐free survival; DCR, disease control rate; PD‐L1, programmed death‐ligand 1; OS, overall survival; PFS, progression‐free survival; HR, hazard ratio; CI, confidence interval; TKI, tyrosine kinase inhibitor; ABCP, Atezolizumab + Carboplatinc + Paclitaxeld + Bevacizumab; ACP, Atezolizumab + Carboplatinc + Paclitaxeld; BCP, Bevacizumab + Carboplatinc + Paclitaxeld; wk, week; AE, adverse event; NA, not applicable.