Multicenter retrospective study of SCLC transformation in EGFR-mutant NSCLC

Histologic transformation to small cell lung cancer (SCLC) is a resistance mechanism to EGFR TKI therapy in EGFR-mutant non-small cell lung cancer (NSCLC). Real-world data on this population are limited. A retrospective cohort study at 26 centers in Turkey (2016-2025) included 59 patients with EGFR-mutant NSCLC and biopsy-proven SCLC transformation (median age 57.8 years; 52.5% male, 76.3% exon 19 deletion). Median progression-free survival (PFS) before transformation was 14.0 months (95% CI 11.3-16.7), median time to transformation was 22.0 months (range 3-110). Following transformation, 54 patients (91.5%) received systemic therapy: carboplatin plus etoposide (CE) alone in 37 (68.5%) and CE plus immunotherapy (atezolizumab, durvalumab, or durvalumab plus osimertinib) in 16 patients (29.6%). Objective response rate was 37.8% with CE alone versus 71.4% with CE plus immunotherapy. Median overall survival (OS) was 41 months from first diagnosis, 38 months from metastatic stage, and 11 months post-transformation. The median OS post-transformation was significantly longer with CE plus immunotherapy versus CE alone (17.0 versus 9.0 months; HR 0.327; p=0.026). The authors conclude that in this large multicenter cohort, adding immunotherapy to CE was associated with improved post-transformation survival.