Immune checkpoint inhibitors + chemotherapy ± anti-VEGF antibodies for EGFR mutant NSCLC
| Treatment | Study name | Setting | Drugs | Phase | Efficacy | AEs | References |
|---|---|---|---|---|---|---|---|
| Chemotherapy + IO | CheckMate012 | 2nd | Nivolumab + platinum doublet | I | EGFR mutated vs. wild type, ORR: 17% vs. 47%, PFS: 4.8 months vs. 7.5 months, OS: 20.5 months vs. 24.5 months. | G3–4: 50%, G5: 0%. (All patients, not only EGFR). | [50] |
| IMpower130 | 2nd | Comparing CBDCA + nab-PTX + atezolizumab with CBDCA + nab-PTX | III | In the subgroup of EGFR/ALK, the mPFS was 7.0 months vs. 6.0 months (HR 0.75, 95% CI: 0.36–1.54). | G3–4: 81% in the combination arm. (All patients, not only EGFR). | [51] | |
| CheckMate722 | 2nd | Nivolumab plus chemotherapy vs. chemotherapy | III | PFS: 5.6 months in the nivolumab plus chemotherapy group and 5.4 months in the chemotherapy group. | G3–4: 45% in nivolumab-based therapy and 29% in chemotherapy. | [55] | |
| KEYNOTE789 | 2nd | Pembrolizumab plus chemotherapy vs. chemotherapy | III | PFS: 5.6 months in the pembrolizumab plus chemotherapy group and 5.5 months in the chemotherapy group. | G3 ≤ TRAE; 43.7%, irAE 4.5% in combination arm. | [56] | |
| Chemotherapy + dual-IO | ILLUMINATE | 2nd | Durvalumab and tremelimumab plus platinum-pemetrexed | II | The ORR was 42% in cohort 1 and 35% in cohort 2, with mPFS of 6.5 months and 4.9 months. | G3–4 colitis 8%, hepatitis 4%, ILD 1%. | [54] |
| Chemotherapy + IO + anti-VEGF | IMpower150 | 2nd | Atezolizumab, bevacizumab, carboplatin-paclitaxel (CP). Control arm: BCP, study arm: ACP, ABCP | III | ORR 70.6% for ABCP, 35.6% for ACP, 41.9% for BCP. | G3–4: 64% of ABCP, 68% of ACP, and 64% of BCP. | [57, 58] |
| Chemotherapy + IO + anti-VEGF | ORIENT | 2nd | Scintilimab, IBI305 (bevacizumab biosimilar), pemetrexed + cisplatin (PC). Arm A: SIPC, arm B: SPC, arm C: PC→S | III | Confirmed ORR were 43.9%, 33.1%, and 25.2% in arm A, B, and C, PFS 6.9 months for arm A, 5.5 months for arm B, 4.3 months for arm C. | Grade ≥ 3 treatment-emergent AEs were 54.7% (arm A), 39.3% (arm B), and 51.0% (arm C). | [55] |
| Chemotherapy + IO + anti-VEGF | IMpower151 | 2nd | Atezolizumab, bevacizumab, carboplatin-pemetrexed. Control arm: bevacizumab + carboplatin-pemetrexed, study arm: atezolizumab + carboplatin-pemetrexed, atezolizumab + bevacizumab + carboplatin-pemetrexed. Over half of the patients had EGFR/ALK | III | In the subgroup of EGFR/ALK, the mPFS was 8.5 months (95% CI: 6.9–10.3) for atezolizumab + bevacizumab + carboplatin-pemetrexed and 8.3 months (95% CI: 6.9–10.1) for bevacizumab + carboplatin-pemetrexed (HR 0.86, 95% CI: 0.55–1.19). | G3–4: 67.1% of ABCP, G5 5.9% in ABCP. | [59] |
irAE: immune-related adverse events; CP: carboplatin-paclitaxel; BCP: bevacizumab carboplatin-paclitaxel; ACP: atezolizumab carboplatin-paclitaxel; PC: pemetrexed + cisplatin; SIPC: scintilimab + IBI305 + pemetrexed + cisplatin; SPC: scintilimab + pemetrexed + cisplatin; EGFR: epidermal growth factor receptor; TRAE: treatment related adverse event; mPFS: median progression free survival; ORR: objective response rate; IO: immune-oncology; OS: overall survival; CBDCA: carboplatin; nab-PTX: nanoparticle albumin-bound paclitaxel; VEGF: vascular endothelial growth factor; NSCLC: non-small cell lung cancer; HR: hazard ratio; CI: confidence intervals; TRAE: treatment related adverse event; ILD: interstitial lung disease; ALK: anaplastic lymphoma kinase. PC→S: pemetrexed + cisplatin → sincilimab