Table 1.
Key clinical trials reporting efficacy and toxicity of PD-1/PD-L1 blockade immunotherapy in EGFR-mutant NSCLC patients.
| PD-1/PD-L1 blockade therapy | Clinical trial # | Efficacy | Toxicity | Reference |
|---|---|---|---|---|
| Atezolizumab | OAK (Phase III; NCT02008227) |
No OS benefit from atezolizumab over docetaxel in EGFR mutant versus wild-type patients (HR: EGFR mutant – 1.24 (0.71-2.18) versus EGFR wild-type – 0.69 (0.57-0.83) | Grade 3-4 treatment-related adverse events: 15% with atezolizumab group versus 43% with docetaxel group | (11) |
| Nivolumab | CheckMate 057 (Phase III; NCT01673867) |
Median OS was 12.2 months (n=292) in nivolumab group versus 9.4 months in docetaxel group (n=290). However, subgroup analysis in EGFR mutated patients did not show PFS or OS benefit from nivolumab (HR=1.18 (0.69-2.00)). | Grade 3-5 treatment related adverse events were reported in 10% of nivolumab and 54% of docetaxel-treated patients | (9) |
| Pembrolizumab | KEYNOTE-010 (Phase III; NCT01905657) |
No OS benefit from pembrolizumab over docetaxel in EGFR mutant versus wild-type patients (HR: EGFR mutant – 0.88 (0.45-1.70) versus EGFR wild-type 0.66 (0.55-0.80)) | Grade 3-5 treatment-related adverse events: 13% with pembrolizumab group versus 35% with docetaxel group | (46) |
| Pembrolizumab | Phase II; NCT0287994 |
The efficacy of pembrolizumab was evaluated in TKI-naïve NSCLC patients with EGFR mutation and PD-L1 positive tumors. None of the patients with EGR-mutant NSCLC responded. Enrollment was ceased due to lack of efficacy after 11 of the 25 planned patients were treated. | -- | (49) |
| Nivolumab, Pembrolizumab, Atezolizumab | Pooled analysis (CheckMate 057, KEYNOTE 010 and POPLAR) | PD-1/PD-L1 blockade immunotherapy did not enhance OS versus docetaxel in advanced NSCLC patients bearing EGFR mutation (n=186, HR=1.05, 95% CI: 0.70-1.55, P<0.81) | -- | (47) |
| Nivolumab, pembrolizumab, atezolizumab | Pooled analysis (CheckMate 017, 057, 063, 003) | PD-1/PD-L1 blockade immunotherapy prolonged OS in EGFR wild-type subgroup (HR=0.67; 95% CI: 0.60=0.75; P<0.001) but not in EGFR mutant subgroup (HR=1.11; 95% CI: 0.80-1.53; P=0.54) | -- | (50) |
CI, confidence interval; HR, hazard ratio; OS, overall survival; PD-1, Programmed death-1; PD-L1, Programmed death ligand-1.