Atezolizumab and bevacizumab plus chemotherapy versus chemotherapy in non-small cell lung cancer after tyrosine kinase inhibitor failure

Background: Determining an optimal treatment strategy after tyrosine kinase inhibitor (TKI) failure remains challenging in oncogene-driven non-small cell lung cancer (NSCLC). Objectives: We aimed to evaluate and compare the efficacy and safety of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) versus pemetrexed plus carboplatin or cisplatin (PC) in patients with progressive NSCLC harboring EGFR , ALK , or ROS1 alterations after TKI failure. Design: Multicenter retrospective study. Methods: We analyzed 114 patients with NSCLC treated with either ABCP ( n = 48) or PC ( n = 66) post-TKI failure between November 2016 and July 2023. Treatment response, progression-free survival (PFS), overall survival (OS), and safety profiles were assessed. Results: Among 106 evaluable participants, the ABCP arm demonstrated a higher response rate (50.0%) than the PC arm (35.0%). During the median follow-up of 29.9 months, PFS was significantly prolonged in the ABCP arm compared with that in the PC arm (7.3 vs 3.0 months, respectively; hazard ratio (HR) 0.643; p = 0.026), whereas OS showed no significant difference ( p = 0.165). Subgroup analysis revealed notable improvements in PFS (7.2 vs 2.1 months, HR 0.235; p < 0.001) and OS (11.0 vs 4.1 months, HR 0.418; p = 0.001) in patients with three or more metastatic sites. Conclusion: ABCP significantly improved PFS compared with PC in patients with NSCLC that progressed despite prior TKI therapy. An OS benefit was observed in patients with three or more metastatic sites.