Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR‐mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis

Abstract Background Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR ‐mutated non‐small cell lung cancer (NSCLC), particularly those lacking the EGFR T790M . IMpower 150 study demonstrated promising efficacy for a combination of immune‐chemotherapy and bevacizumab in patients with EGFR ‐mutated NSCLC. Methods This open‐label, single‐arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.5 mg/kg) and chemotherapy in patients with EGFR ‐mutated NSCLC following TKI failure. The primary endpoint was objective response rate (ORR). The re‐biopsy tissue specimens and serial peripheral blood samples were collected to analyse the immune cell profile and tumour microenvironments. Rresults 22 EGFR ‐mutant NSCLC patients participated in this study. The ORR was 42.9%, with a disease control rate (DCR) of 100%. Median progression‐free survival (PFS) was 6.3 months. Patients with programmed death‐ligand 1 (PD‐L1) expression ≥1% exhibited significantly higher ORR (75 vs. 23.1%; p = .032) and longer PFS (14.0 vs. 6.1 months; p = .022) compared with those with PD‐L1 expression < 1%. Grade ≥ 3 adverse events occurred in 40.9% of patients. Higher peritumour nature killer (NK) cell infiltration and lower peripheral helper T cell counts before treatment were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9 + myelod‐derived suppressor cells (MDSCs) increased, while regulatory T cells decreased. Conclusion This modified combination regimen may be a promising therapeutic option for EGFR ‐mutant NSCLC patients with TKI resistance, especially those with PD‐L1‐positive tumours. Furthermore, immune cell profiling may aid in identifying patients who may benefit from this approach. Key points The combination regimen yielded promising efficacy in NSCLC patients after EGFR‐TKI resistance, particularly those with PD‐L1‐positive tumours. Higher peritumour NK cell and lower peripheral helper T cell were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9 + MDSC increased, but Treg cells decreased.