Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Akihiro Yoshimura, Tadaaki Yamada, Yusuke Okuma, Akito Fukuda, Satoshi Watanabe, Naoya Nishioka, Takayuki Takeda, Yusuke Chihara, Shinnosuke Takemoto, Taishi Harada, Osamu Hiranuma, Yukina Shirai, Akihiro Nishiyama, Seiji Yano, Yasuhiro Goto, Shinsuke Shiotsu, Kei Kunimasa, Yoshie Morimoto, Masahiro Iwasaku, Yoshiko KanekoJunji Uchino, Hirotsugu Kenmotsu, Toshiaki Takahashi, Koichi Takayama

研究成果: Article査読

3 被引用数 (Scopus)

抄録

Background: Osimertinib monotherapy is currently the standard of care as a first-line treatment for patients harboring epidermal growth factor receptor (EGFR) mutations; however, some EGFR-mutated non-small cell lung cancer (NSCLC) patients exhibit primary resistance and an insufficient response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Elevated programmed death-ligand 1 (PD-L1) expression in tumors was reported as a negative predictive factor for outcomes of first- or second-generation EGFR-TKIs. Methods: We prospectively assessed advanced NSCLC patients with EGFR mutations who were treated with osimertinib at 14 institutions in Japan between September 2019 and December 2020. Relationships between outcomes of osimertinib monotherapy and patients’ characteristics were reviewed. Results: Seventy-one patients who underwent the tumor PD-L1 test were enrolled. Multivariate analysis identified tumor PD-L1 expression as an independent predictor for progression-free survival (PFS) with osimertinib treatment (P=0.029). The objective-response and disease-control rates for osimertinib treatment were significantly lower in patients demonstrating elevated PD-L1 levels relative to those with low or negative PD-L1 level (P=0.043 and P=0.007, respectively). Furthermore, among patients treated with osimertinib, those with high PD-L1 levels exhibited shorter PFS relative to those with low plus negative PDL1 level (median PFS: 5.0 vs. 17.4 months; P<0.001). Conclusions: Elevated tumor PD-L1 expression is associated with poor outcomes of osimertinib monotherapy in previously untreated advanced NSCLC patients with EGFR mutation. Further clinical trials are warranted to accumulate evidence demonstrating the effectiveness of combination therapy with osimertinib for EGFR-mutated advanced NSCLC patients with elevated tumor PD-L1 expression. Trial Registration: UMIN000043942.

本文言語English
ページ(範囲)3582-3593
ページ数12
ジャーナルTranslational Lung Cancer Research
10
8 August
DOI
出版ステータスPublished - 08-2021

All Science Journal Classification (ASJC) codes

  • 腫瘍学

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