Impact of Subsequent Treatment on Clinical Outcomes in Patients with EGFR-Mutant Non-Small Cell Lung Cancer Transformed to Small-Cell Lung Cancer.

Purpose: In epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with EGFR-tyrosine kinase inhibitors (TKIs), transformation to small-cell lung cancer (SCLC) is associated with poor outcomes, and the optimal treatment strategy is unclear. This study aimed to investigate the clinical factors and treatments associated with outcomes in this group.

Patients and methods: This retrospective multicenter study enrolled patients with SCLC transformed from advanced NSCLC after progression on EGFR-TKI treatment. We analyzed clinical and demographic characteristics, first-line EGFR-TKI treatments, and subsequent regimens to identify factors associated with clinical outcomes.

Results: Twenty-seven patients diagnosed with SCLC transformation after EGFR-TKI therapy between 2018 and 2023 were enrolled, most of whom had an EGFR exon 19 deletion (67%). The subsequent treatment regimens included traditional chemotherapy (CT) in 12 patients (44%), combined CT/EGFR-TKI in 10 patients (37%), and combined CT/immunotherapy in 5 patients (19%). The median progression-free survival (PFS) with first-line EGFR-TKI treatment, subsequent SCLC treatment, and overall survival (OS) were 16.1 months, 6.4 months, and 39.5 months, respectively. The overall response rate (ORR), disease control rate (DCR), and median PFS for subsequent treatments were 38.5%, 69.2%, and 6.4 months, respectively. The DCRs for subsequent CT, CT/TKI, and CT/immunotherapy were 41.7%, 88.9%, and 100%, respectively. ORR and PFS were higher in the CT/TKI (44.4% and 7.2 months) and CT/immunotherapy (80.0% and 11.3 months) groups compared to CT (16.7% and 3.7 months), but these differences were not statistically significant. Univariate and multivariate analyses showed no significant differences in PFS and OS among treatments.

Conclusion: In patients with SCLC transformed from advanced NSCLC after EGFR-TKI treatment, adding immunotherapy and EGFR-TKI to CT improved DCR and showed trends in ORR and PFS, but did not provide an OS benefit. More prospective studies with varied therapeutic approaches are needed to confirm these findings.