Impact of Thyroid Transcription Factor‐1 Expression on Outcomes of Platinum‐Based Chemoimmunotherapy in Advanced or Recurrent Non‐Squamous Non‐Small Cell Lung Cancer

BACKGROUND: Thyroid transcription factor-1 (TTF-1) is a diagnostic biomarker in non-squamous (non-sq) non-small cell lung cancer (NSCLC). TTF-1 negativity has been associated with poor outcomes following immunotherapy and pemetrexed-based chemotherapy in advanced non-sq NSCLC. However, the impact of TTF-1 expression on chemoimmunotherapy efficacy regimens remains unclear. METHODS: We retrospectively analyzed patients with advanced or recurrent non-sq NSCLC who received first-line platinum and pemetrexed plus pembrolizumab (Platinum/PEM/Pembro) or carboplatin and nab-paclitaxel plus atezolizumab (CBDCA/nab-PTX/Atezo) between March 2019 and May 2025 at our institution. RESULTS: Among 67 patients, 44 were TTF-1 positive and 23 were TTF-1 negative. In the overall cohort, TTF-1-positive patients had significantly longer progression-free survival (PFS) and overall survival (OS) than TTF-1-negative patients. In the Platinum/PEM/Pembro group, PFS and OS did not differ by TTF-1 status (median PFS: 8.5 vs. 7.0 months; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.39-1.86, and median OS: 23.7 vs. 26.1 months; HR, 0.93; 95% CI, 0.36-2.35). In univariate analysis of the overall population, TTF-1 expression and performance status (PS) were significantly associated with PFS, while TTF-1 expression, PS, and histological type were significantly associated with OS. The Platinum/PEM/Pembro group had a higher relative dose intensity of concomitant chemotherapy, a greater median number of immune checkpoint inhibitor cycles, and a longer median treatment duration. Immune-related adverse events (irAEs) were more frequent with Platinum/PEM/Pembro (50.0% vs. 17.4%, p = 0.0164). CONCLUSIONS: Platinum/PEM/Pembro may be a therapeutic option for TTF-1-negative non-sq NSCLC with good PS and adenocarcinoma histology, although careful management of irAE is required.