Predictive value of TTF-1 expression for stratifying outcomes between dual ICI and chemoimmunotherapy in patients with PD-L1-negative NSCLC.

Authors

Naoya Nishioka, Daiki Murata, Koichi Azuma, Kazuhiro Ito, Takashi Nomizo, Kazuhiko Yamada, Tatsuya Imabayashi, Kentaro Iwanaga, Kenji Chibana, Takayo Ota, Yuuya Nishii, Akira Nakao, Asuka Okada, Kosuke Hamai, Takenori Sakai, Taishi Harada, Keiko Tanimura, Kohei Yoshimine, Yosuke Tamura, Ryuichiro Takaki, Yasuhiro Goto, Makoto Hibino, Tomohiro Oba, Toshiyuki Sumi, Hiroyasu Kaneda, Tadaaki Yamada, Koichi Takayama

Published in

International journal of clinical oncology. Aug 04, 2026. Epub Aug 04, 2026.

Abstract

Thyroid transcription factor-1 (TTF-1) has emerged as a novel predictive biomarker associated with the prognosis and treatment response of non-squamous non-small-cell lung cancer (NSCLC) to cytotoxic chemotherapy. This study evaluated the clinical significance of TTF-1 expression in advanced NSCLC with programmed death-ligand 1 (PD-L1) < 1%, with a specific focus on its utility in stratifying treatment outcomes between dual immune checkpoint inhibitor (IO-IO) therapy and chemoimmunotherapy.
We conducted a multicenter retrospective study across 22 Japanese institutions, evaluating 194 patients with advanced or recurrent non-squamous NSCLC and PD-L1 < 1% treated with IO-IO therapy or chemoimmunotherapy between 2019 and 2022. Survival outcomes were analyzed using multivariable Cox regression.
TTF-1-positive patients had significantly longer progression-free survival (PFS) and overall survival (OS) than TTF-1-negative patients [adjusted hazard ratio (HR) for PFS: 0.65, p = 0.009; adjusted HR for OS: 0.69, p = 0.04]. Among TTF-1-positive patients, no significant difference in survival was observed between IO-IO therapy and chemoimmunotherapy. By contrast, TTF-1-negative patients experienced significantly improved outcomes with chemoimmunotherapy than with IO-IO therapy (adjusted HR for PFS: 0.37, p = 0.01; adjusted HR for OS: 0.39, p = 0.02).
TTF-1 expression may serve as a prognostic and potentially predictive biomarker in PD-L1-negative NSCLC patients. TTF-1-negative patients appeared to derive greater benefit from the addition of chemotherapy. These findings suggest that TTF-1 expression may have potential utility in guiding treatment selection and warrant prospective validation.

PMID:
42552404
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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