TY - JOUR
T1 - Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer
T2 - a prospective observational study
AU - Yoshimura, Akihiro
AU - Yamada, Tadaaki
AU - Okuma, Yusuke
AU - Fukuda, Akito
AU - Watanabe, Satoshi
AU - Nishioka, Naoya
AU - Takeda, Takayuki
AU - Chihara, Yusuke
AU - Takemoto, Shinnosuke
AU - Harada, Taishi
AU - Hiranuma, Osamu
AU - Shirai, Yukina
AU - Nishiyama, Akihiro
AU - Yano, Seiji
AU - Goto, Yasuhiro
AU - Shiotsu, Shinsuke
AU - Kunimasa, Kei
AU - Morimoto, Yoshie
AU - Iwasaku, Masahiro
AU - Kaneko, Yoshiko
AU - Uchino, Junji
AU - Kenmotsu, Hirotsugu
AU - Takahashi, Toshiaki
AU - Takayama, Koichi
N1 - Publisher Copyright:
© Translational Lung Cancer Research. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85114053311&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85114053311&partnerID=8YFLogxK
U2 - 10.21037/tlcr-21-461
DO - 10.21037/tlcr-21-461
M3 - Article
AN - SCOPUS:85114053311
SN - 2226-4477
VL - 10
SP - 3582
EP - 3593
JO - Translational Lung Cancer Research
JF - Translational Lung Cancer Research
IS - 8 August
ER -
