Exploration of clinical Biomarkers for guiding treatment selection between chemotherapy and combination therapy with Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in EGFR-Mutant NSCLC patients after EGFR-TKI Therapy: The SPIRAL-STEP study

Objectives: In patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations, a chemoimmunotherapy regimen of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) has shown promising outcomes following treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, evidence on whether ABCP provides a survival advantage over platinum-based chemotherapy in real-world clinical settings remains limited. This study aimed to investigate the efficacy and safety of ABCP versus platinum-based chemotherapy in patients with EGFR-mutant NSCLC who underwent EGFR-TKI treatment. Materials and methods: We retrospectively assessed consecutive patients with EGFR-mutant-NSCLC who received platinum-based chemotherapy or ABCP after EGFR-TKI treatment at 20 institutions in Japan between January 2017 and July 2022. Results: Overall, 408 patients with advanced or recurrent EGFR-mutant NSCLC were analyzed. A total of 306 patients (75.0 %) received chemotherapy (Chemo) or chemotherapy plus bevacizumab (Chemo + BEV), and 102 patients (25.0 %) received ABCP. After propensity score matching, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between the Chemo or Chemo + BEV and ABCP groups (6.0 months versus 7.2 months, log-rank test; p = 0.44 and 22.5 months versus 21.3 months, p = 0.84, respectively). Limiting to the programmed cell death-ligand 1 (PD-L1) ≥ 50 % cohort, the ABCP group had a significantly longer PFS than did the Chemo or Chemo + BEV group (7.9 months versus 4.8 months, log-rank test; p = 0.02). Conclusion: In patients with EGFR-mutant NSCLC previously treated with EGFR-TKI, ABCP achieved comparable outcomes to those of platinum-based chemotherapy. Among patients with high PD-L1 expression, ABCP may be a superior treatment option.