Abstract
Background Thyroid transcriptional factor-1 (TTF-1) is associated with the development of interstitial lung disease (ILD) and is a mutational target in lung adenocarcinoma with ILD. TTF-1 expression is also associated with the efficacy of pemetrexed-based chemotherapy for non-squamous non-small cell lung cancer (NS-NSCLC). However, the relationship between TTF-1 expression and the efficacy of immunotherapy using programmed cell death 1 inhibitor (PD-1i), especially in lung cancer patients with ILD, remains unclear.
Methods Medical data of NS-NSCLC patients treated with PD-1i at multiple centres were analysed retrospectively. Patients were divided into those with or without concomitant ILD, with the two cohorts further stratified by TTF-1 expression.
Results The study population included 62 NS-NSCLC patients, 34 with and 28 without ILD. Median progression-free survival (PFS) during PD-1i treatment was significantly shorter in TTF-1-negative than -positive patients (2.0 versus 12.1 months, p=0.004) in the ILD cohort but did not differ significantly in the non-ILD cohort (1.8 versus 2.6 months, p=0.63). Median overall survival (OS) was also significantly shorter in TTF-1-negative than -positive patients in the ILD cohort (14.5 versus 42.5 months, p=0.018) but not in the non-ILD cohort (33.7 versus 37.1 months, p=0.53). Cox regression analyses showed that absence of TTF-1 expression was an independent risk factor for PFS (hazard ratio [HR] 2.75, p=0.024) and OS (HR 2.81, p=0.012) in the ILD cohort.
Conclusion TTF-1 expression in NS-NSCLC patients with ILD may predict prognosis when treated with PD-1i.
Footnotes
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Conflict of interest: Masaru Ito: Declarations of interest: none.
Conflict of interest: Takayuki Honda: Declarations of interest: Dr. Takayuki Honda reports lecture fees from Ono Pharmaceutical Co., Ltd. and AstraZeneca K.K. outside the submitted work.
Conflict of interest: Iichiroh Ohnishi: Declarations of interest: none.
Conflict of interest: Satoshi Endo: Declarations of interest: none.
Conflict of interest: Akifumi Mochizuki: Declarations of interest: none.
Conflict of interest: Naoki Nishiyama: Declarations of interest: none.
Conflict of interest: Rie Sakakibara: Declarations of interest: none.
Conflict of interest: Susumu Takahashi: Declarations of interest: none.
Conflict of interest: Takashi Kumagai: Declarations of interest: none.
Conflict of interest: Koki Hata: Declarations of interest: none.
Conflict of interest: Sao Yoshii: Declarations of interest: none.
Conflict of interest: Kentaro Nakamura: Declarations of interest: none.
Conflict of interest: Takaaki Yamashita: Declarations of interest: none.
Conflict of interest: Yoshikazu Tsukada: Declarations of interest: none.
Conflict of interest: Tomoshige Chiaki: Declarations of interest: none.
Conflict of interest: Yoshihiro Miyashita: Declarations of interest: none.
Conflict of interest: Ichirou Natsume: Declarations of interest: none.
Conflict of interest: Kazuhito Saitou: Declarations of interest: none.
Conflict of interest: Yasunari Miyazaki: Declarations of interest: Dr. Yasunari Miyazaki reports lecture fees from Ono Pharmaceutical Co., Ltd., MSD K.K., and AstraZeneca K.K. outside the submitted work.
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- Received June 21, 2024.
- Accepted August 19, 2024.
- Copyright ©The authors 2024
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