Table 4.
Clinical data on anti-PD1 efficacy in NSCLC with actionable oncogenic driver alterations.
| Study | Main Results | Ref. | |
|---|---|---|---|
| Randomized Clinical Trials | |||
| CheckMate 057 | Nivolumab vs. Docetaxel |
EGFR (n = 82): HR 1.38 (0.69–2) | [61] |
| ALK (n = 21): no subgroup analysis | |||
| Keynote 010 | Pembrolizumab vs. Docetaxel |
EGFR (n = 86): HR 0.89 (0.45–1.70) | [62] |
| ALK (n = 8): no subgroup analysis | |||
| OAK | Atezolizumab vs. Docetaxel |
EGFR (n = 85): HR 1.24 (0.71–2.18) | [63] |
| ALK (n = 2): no subgroup analysis | |||
| Atlantic (phase II) | Durvalumab | EGFR/ALK (n = 107) | [104] |
| ORR: 16%, OS: 12.3, PFS 1.9 | |||
| IMPOWER 150 | AtezolizumabBCP vs. BCP |
EGFR (n = 79): | [100,101] |
| HR for OS 0.61 (0.36–1.03) | |||
| Subgroup previously treated by TKI (n = 50): HR for OS 0.39 (0.14–1.07); HR for PFS 0.42 (0.22–0.80) | |||
| ALK (n = 31): no subgroup analysis | |||
| Real-world Studies | |||
| Gainor, 2016 | 28 EGFR/ALK+ vs. 30 WT |
RR 3.6% vs. 23.3% | [87] |
| Dudnik, 2018 | 12 BRAF V600E | RR 25%, PFS 3.7 (1.6–6.6) | [86] |
| 10 other BRAF | RR 33% PFS 4.1 (0.1–19.6) | ||
| Sabari, 2018 | 24 METex14 | RR 17% (6–36), PFS 1.9 (1.7–2.7) | [80] |
| Rizvi, 2018 | 17 EGFR, 7 ROS1, 9 BRAF, 2 ALK, 2 RET | Durable clinical benefit in 2 EGFR, 4 BRAF, 2HER2 and 1 ROS1 patients | [64] |
| Liu, 2018 | 6 EGFR1 1 ALK | 1 EGFR with partial response | [73] |
| Garassino, 2018 | 102 EGFR+ vs. 1293 WT |
RR 8.8% vs. 19.6% * | [105] |
| OS 8.3 vs. 11.0 * | |||
| Wei-Chu, 2018 | 26 HER2 | RR 12%, PFS 1.9, OS 10.4 | [84] |
| Mazieres, 2019 | 125 EGFR | RR 12%, PFS 2.1 | [83] |
| 43 BRAF | RR 24%, PFS 3.1 | ||
| 36 MET | RR 16%, PFS 3.4 | ||
| 29 HER2 | RR 7%, PFS 2.5 | ||
| 23 ALK | RR 0%, PFS 2.5 | ||
| 16 RET | RR 6%, PFS 2.1 | ||
| 7 ROS1 | RR 17% | ||
| Morita, 2019 | 116 EGFR | OS 12.1 vs. 14.6 * PFS 1.5 vs. 2.3 * RR 8.6% vs. 22.6 * |
[106] |
| Bylicki, 2020 | 42 EGFR | OS 13.9 (8.8–20), PFS 2.2 (1.4–3.2) | |
| 8 ALK | OS 19.2 (13.1-NR), PFS 2.4 (2.1-NR) | ||
| 1 ROS1 | OS 2.8, PFS 1.4 | ||
| Barlesi, 2020 | 44 EGFR | OS 8.1 vs. 12.2 | [107] |
| Guisier, 2020 | 26 BRAF V600 | RR 26%, PFS 5.3, OS 22.5 | [85] |
| 18 BRAF NV600 | RR 35%, PFS 5.3, OS 12 | ||
| 30 MET | RR 36%, PFS 4.9, OS 13.4 | ||
| 23 HER 2 | RR 27%, PFS 2.2, OS 20.4 | ||
| 9 RET | RR 37%, PFS 7.6, OS NR | ||
| Lau, 2021 | 28 EGFR SM | RR 11%, PFS 1.7, | [79] |
| 6 EGFR-Ex20ins | RR 50%, PFS 4.8, | ||
| 14 HER 2 | RR 29%, PFS 3.6 | ||
| Chen, 2021 | 9 EGFR-Ex20ins | RR 22% | [78] |
| 6 HER2-Ex20ins | RR 0% | ||
| Yamada, 2021 | 20 common EGFR | RR 10%, PFS 1.6 | [102] |
| 7 uncommon EGFR | RR 57%, PFS 8.5 | ||
BCP: Bevacizumab + carboplatin + paclitaxel, SM: sensitizing mutations, WT: wild-type, RR: response rate, PFS: progression-free survival, OS: overall survival. PFS and OS are given in months. * comparisons are shown between EGFR-mutated and EGFR wild type NSCLC patients.