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Multicenter Study
. 2024 Jul 15:15:1399889.
doi: 10.3389/fimmu.2024.1399889. eCollection 2024.

Unraveling the influence of TTF-1 expression on immunotherapy outcomes in PD-L1-high non-squamous NSCLC: a retrospective multicenter study

Naoya Nishioka  1 , Hayato Kawachi  1 , Tadaaki Yamada  1 , Motohiro Tamiya  2 , Yoshiki Negi  3 , Yasuhiro Goto  4 , Akira Nakao  5 , Shinsuke Shiotsu  6 , Keiko Tanimura  7 , Takayuki Takeda  7 , Asuka Okada  8 , Taishi Harada  9 , Koji Date  10 , Yusuke Chihara  11 , Isao Hasegawa  12 , Nobuyo Tamiya  13 , Taiki Masui  1 , Natsuki Sai  1 , Masaki Ishida  1 , Yuki Katayama  1 , Kenji Morimoto  1 , Masahiro Iwasaku  1 , Shinsaku Tokuda  1 , Takashi Kijima  3 , Koichi Takayama  1
Affiliations
Multicenter Study

Unraveling the influence of TTF-1 expression on immunotherapy outcomes in PD-L1-high non-squamous NSCLC: a retrospective multicenter study

Naoya Nishioka et al. Front Immunol. .

Abstract

Introduction: Several studies explored the association between thyroid transcription factor-1 (TTF-1) and the therapeutic efficacy of immunotherapy. However, the effect of TTF-1 on the therapeutic efficacy of programmed death-1 (PD-1) inhibitor/chemoimmunotherapy in patients with non-squamous non-small cell lung cancer (non-Sq NSCLC) with a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or more who are highly susceptible to immunotherapy remains unresolved. Therefore, we evaluated whether TTF-1 has a clinical impact on this population.

Methods: Patients with non-Sq NSCLC and high PD-L1 expression who received PD-1 inhibitor monotherapy or chemoimmunotherapy between May 2017 and December 2020 were retrospectively enrolled. Treatment efficacy was compared after adjusting for baseline differences using propensity score matching.

Results: Among the 446 patients with NSCLC with high PD-L1 expression, 266 patients with non-Sq NSCLC were analyzed. No significant differences in therapeutic efficacy were observed between the TTF-1-positive and -negative groups in the overall and propensity score-matched populations. Of chemoimmunotherapy, pemetrexed containing regimen significantly prolonged progression-free survival compared to chemoimmunotherapy without pemetrexed, regardless of TTF-1 expression (TTF1 positive; HR: 0.46 (95% Confidence interval: 0.26-0.81), p<0.01, TTF-1 negative; HR: 0.29 (95% Confidence interval: 0.09-0.93), p=0.02).

Discussion: TTF-1 expression did not affect the efficacy of PD-1 inhibitor monotherapy or chemoimmunotherapy in patients with non-Sq NSCLC with high PD-L1 expression. In this population, pemetrexed-containing chemoimmunotherapy demonstrated superior anti-tumor efficacy, irrespective of TTF-1 expression.

Keywords: PD-L1; TTF-1; antitumor efficacy; immunotherapy; non-squamous non-small cell lung cancer.

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Conflict of interest statement

NN received personal fees from Chugai Pharmaceutical Co. Ltd., AstraZeneca KK., Eli Lilly Japan KK, and MSD KK outside the purview of the submitted work. HK received personal fees from Ono Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Eli Lilly Japan KK, and MSD KK outside the purview of the submitted work. TY received research grants from Ono Pharmaceutical, Janssen, AstraZeneca, and Takeda Pharmaceutical and has received speaking honoraria from Eli Lilly and Chugai Pharmaceutical outside the purview of the submitted work. MT received research grants from Boehringer Ingelheim, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Daiichi-Sankyo, Eisai, Chugai Pharmaceutical and Janssen, and personal fees from Chugai Pharmaceutical, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Novartis, Pfizer, Asahi Kasei Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Bayer, Amgen, Kyowa-Kirin, and Nippon Kayaku, outside the purview of the submitted work. AO has received personal fees from Chugai-Roshe, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Japan, Nippon Kayaku, and Bristol Myers Squibb outside the purview of the submitted work. TK received personal fees from Chugai Pharmaceutical Co., Ltd. and MSD KK outside the purview of the submitted work. KCT received research grants from Chugai Pharmaceutical and Ono Pharmaceutical and personal fees from AstraZeneca, Chugai Pharmaceutical, MSD-Merck, Eli Lilly, Boehringer-Ingelheim, and Daiichi-Sankyo outside the purview of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of treatment efficacy between TTF-1 positive and negative groups in the overall population. Kaplan–Meier curves for (A) progression-free survival (PFS) and (B) overall survival (OS) in the entire population. PFS (C, D) OS in the Pembrolizumab monotherapy population and PFS (E, F) OS in the Chemoimmunotherapy population.
Figure 2
Figure 2
Comparison of treatment efficacy between TTF-1 positive and negative groups after propensity matching. Kaplan–Meier curves for (A) progression-free survival (PFS) and (B) overall survival (OS) in the entire population. PFS (C, D) OS in the Pembrolizumab monotherapy population and PFS (E, F) OS in the Chemoimmunotherapy population.
Figure 3
Figure 3
Comparison of treatment efficacy across different treatment regimens stratified by TTF-1 Expression. Kaplan–Meier curves of (A) progression-free survival (PFS) and (B) overall survival (OS) for each treatment regimen in the TTF-1 positive non-squamous NSCLC population, and Kaplan–Meier curves of (C) PFS and (D) OS for each treatment regimen in the TTF-1 negative non-squamous NSCLC population.
See this image and copyright information in PMC

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