TTF-1 Expression and Efficacy of Platinum and Pemetrexed Plus Pembrolizumab in Advanced Lung Adenocarcinoma

Thyroid transcription factor-1 (TTF-1) negativity is a poor prognostic factor for patients with lung adenocarcinoma. Platinum and pemetrexed have inferior therapeutic efficacy compared to other chemotherapy regimens in TTF-1-negative lung adenocarcinomas. However, the association between TTF-1 expression and efficacy of chemotherapy plus immune checkpoint inhibitors remains unclear. The aim of the study was to evaluate whether tumor expression of TTF-1 influence the efficacy of platinum and pemetrexed plus pembrolizumab in patients with advanced adenocarcinoma.

This single-center retrospective study comprised patients with advanced lung adenocarcinoma treated with platinum and pemetrexed plus pembrolizumab and histologically evaluated for TTF-1 expression between January 2019 and June 2025. TTF-1 was detected in tumor tissue samples obtained by surgery, bronchoscopy, or computer tomography-guided biopsy using 8G7G3/1 antibody. We collected clinical medical records including TTF-1 expression and evaluated the relationship between TTF-1 expression and overall response rate, progression-free survival (PFS), and overall survival (OS). The Cox proportional hazards model was used to determine the association between patient background and survival outcomes.

Of the 54 patients, 29 (53.7%) were TTF-1 positive. PFS (median, 12.6 vs. 13.1 months, p=0.92) and OS (median, 33.4 vs. 41.1 months, p=0.92) did not significantly differ between the TTF-1-positive and TTF-1-negative patients. Multivariate analysis revealed that performance status and primary tumor location were significantly associated with shorter OS, whereas TTF-1 negativity was not significantly associated with shorter OS.

Platinum and pemetrexed combined with pembrolizumab remains an effective first-line treatment option for lung adenocarcinoma, regardless of TTF-1 expression.