Efficacy of Tyrosine Kinase Inhibitors in Primary Driver-Gene-Positive Combined Small-Cell Lung Cancer: A Retrospective Study

We evaluated targeted therapy efficacy in gene-mutated combined SCLC to provide new insights into this rare subtype. 31 c-SCLC patients were retrospectively analyzed, comparing treatment outcomes using Kaplan-Meier method. TKIs showed promising efficacy in driver-gene-positive c-SCLC, especially when combined with chemotherapy. Genetic testing and targeted therapy hold potential benefits, urging larger prospective studies in c-SCLC to assess efficacy and feasibility. Background: Combined small-cell lung cancer (c-SCLC) with gene mutations is a rare subtype often found alongside adenocarcinoma. Targeted therapy may be effective because of the presence of specific molecular targets. However, due to its rarity and unconventional genetic testing, the efficacy remains uncertain. Methods: A total of 31 c-SCLC patients with gene mutations were retrospectively included and grouped according to their treatment regimens. Treat-ment outcomes were evaluated. Kaplan-Meier method was used for survival analysis, with Log Rank test applied for comparison between groups. Results: We divided the 31 patients into 3 groups according to first-line treatment: group A (chemotherapy, n = 16), group B (targeted monotherapy, n = 7), and group C (targeted combination therapy, n = 8). The overall response rates (ORR) were 43.8%, 42.9%, and 62.5%. The disease control rates (DCR) were 87.5%, 85.7%, and 100%. The median progression-free survival (PFS) was 4.0, 5.0, and 7.93 months ( P = .024), with a significant difference between group A and C ( P = .010). The median overall survival (OS) was 14.10, 17.43, and 12.93 months ( P = .313). Seven patients in group A received targeted therapy in later-line. Of the total 22 patients received targeted monotherapy or combination therapy, the ORR and DCR were 54.5% and 90.9%. The median PFS and OS were 5.87 and 17.30 months. Additionally, adverse events (AEs) occurred in 53.8% and 88.9% of monotherapy and combination therapy. The most common AEs in monotherapy were elevated transaminases (23.1%) and in combination anemia (66.7%). Conclusions: TKIs showed encouraging efficacy in driver-gene-positive c-SCLC. While monotherapy may be a supplementary option, combination with chemotherapy appears to be preferable and superior.