TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study

Yuki Katayama; Tadaaki Yamada; Kenji Morimoto; Hiroyuki Fujii; Satomi Morita; Keiko Tanimura; Takayuki Takeda; Asuka Okada; Shinsuke Shiotsu; Yusuke Chihara; Osamu Hiranuma; Takahiro Yamada; Takahiro Ota; Taishi Harada; Isao Hasegawa; Akihiro Yoshimura; Masahiro Iwasaku; Shinsaku Tokuda; Young Hak Kim; Koichi Takayama

doi:10.1016/j.jtocrr.2023.100494

TTF-1 Expression and Clinical Outcomes of Combined Chemoimmunotherapy in Patients With Advanced Lung Adenocarcinoma: A Prospective Observational Study

JTO Clin Res Rep. 2023 Mar 7;4(4):100494. doi: 10.1016/j.jtocrr.2023.100494. eCollection 2023 Apr.

Authors

Yuki Katayama¹, Tadaaki Yamada¹, Kenji Morimoto¹, Hiroyuki Fujii¹, Satomi Morita¹, Keiko Tanimura², Takayuki Takeda², Asuka Okada³, Shinsuke Shiotsu⁴, Yusuke Chihara⁵, Osamu Hiranuma⁶, Takahiro Yamada⁷, Takahiro Ota⁸, Taishi Harada⁹, Isao Hasegawa¹⁰, Akihiro Yoshimura¹, Masahiro Iwasaku¹, Shinsaku Tokuda¹, Young Hak Kim¹, Koichi Takayama¹

Affiliations

¹ Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
² Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
³ Department of Respiratory Medicine, Saiseikai Suita Hospital, Osaka, Japan.
⁴ Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.
⁵ Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan.
⁶ Department of Respiratory Medicine, Otsu City Hospital, Shiga, Japan.
⁷ Department of Respiratory Medicine, Matsushita Memorial Hospital, Osaka, Japan.
⁸ Department of Respiratory Medicine, Kyoto city Hospital, Kyoto, Japan.
⁹ Department of Medical Oncology, Fukuchiyama City Hospital, Kyoto, Japan.
¹⁰ Department of Respiratory Medicine, Saiseikai Shigaken Hospital, Shiga, Japan.

Abstract

Introduction: Lung adenocarcinoma with negative TTF-1 expression is believed to be a poor prognostic factor for certain systemic treatments. Nevertheless, the impact of TTF-1 expression on combined chemoimmunotherapy remains unclear. We aimed to investigate the relationship between tumor TTF-1 expression and the efficacy of combined chemoimmunotherapy in patients with advanced lung adenocarcinoma.

Methods: This multicenter prospective observational study included 58 patients with advanced lung adenocarcinoma treated with combined chemoimmunotherapy across 10 institutions in Japan. The expression of TTF-1 in pretreatment tumors was determined using immunohistochemistry.

Results: The objective response rate of combined chemoimmunotherapy was significantly higher in TTF-1-positive groups than in TTF-1-negative groups (p = 0.02). The median progression-free survival (PFS) and overall survival were significantly longer in TTF-1-positive groups than in TTF-1-negative groups (10.9 versus 5.0 mo; p = 0.01). Multivariate analysis revealed that TTF-1 expression was an independent favorable prognostic factor for PFS. Moreover, TTF-1 expression in patients with lung adenocarcinoma is significantly associated with programmed death-ligand 1 expression (p = 0.003). The TTF-1-positive group with programmed death-ligand 1 tumor proportion score greater than or equal to 50% had a significantly longer PFS than the other groups (p = 0.02).

Conclusions: TTF-1 positivity is associated with better clinical outcomes in patients with advanced lung adenocarcinoma treated with combined chemoimmunotherapy.

Keywords: Combined chemoimmunotherapy; Lung adenocarcinoma; PD-L1; Prospective observation study; Thyroid transcription factor 1.