Impact of Thyroid Transcription Factor‐1 Expression on Outcomes of Platinum‐Based Chemoimmunotherapy in Advanced or Recurrent Non‐Squamous Non‐Small Cell Lung Cancer
Ryohei Kamada, Hiroshi Yokouchi, Shohei Mizobuchi, Ken Kuwahara, Yasushi Mizukami, Hidenori Mizugaki, Noriyuki Yamada, Hajime Asahina, Hirofumi Adachi, Yoshihiro Matsuno, Satoshi OizumiABSTRACT
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.