Prognosis following the initiation of various immune checkpoint inhibitor therapies in TTF-1-negative non-small cell lung cancer.

PURPOSE: Even though thyroid transcription factor-1 (TTF-1)-negative non-squamous non-small cell lung cancer (NSCLC) is associated with a poor prognosis, the optimal treatment regimens have not been established. We conducted this multicenter retrospective study to evaluate the association between specific treatment choices and survival outcomes in this population. METHODS: We retrospectively analyzed data from patients with TTF-1-negative non-squamous NSCLC treated with immune checkpoint inhibitors plus chemotherapy between 2019 and 2022. TTF-1 expression levels were assessed by immunohistochemistry performed in routine clinical practice at each participating institution. Patients with EGFR or ALK driver alterations were excluded. Progression-free survival (PFS) and overall survival (OS) were evaluated to compare treatment options, focusing particularly on the use of CTLA-4 antibodies. RESULTS: A total of 58 patients were included in the analysis. Univariate analysis revealed no association between PFS and treatment options, including CTLA-4 antibodies, pemetrexed, and vascular endothelial growth factor (VEGF) inhibitors. Conversely, OS was longer in patients treated with CTLA-4 antibody regimens (p = 0.045, log-rank test). Multivariate analysis showed a hazard ratio of 0.36 (95% confidence interval: 0.12-1.07) for OS in patients receiving CTLA-4 antibody regimens compared with those who did not. CONCLUSION: Although the present study failed to identify the immune checkpoint inhibitor therapy associated with improved survival, it did suggest the hypothesis that CTLA-4 antibody-containing regimens may be effective for patients with TTF-1-negative non-squamous NSCLC.