A Randomized Phase II Study Comparing Nivolumab with Carboplatin–Pemetrexed for EGFR-Mutated NSCLC with Resistance to EGFR Tyrosine Kinase Inhibitors (WJOG8515L)

Hidetoshi Hayashi, Shunichi Sugawara, Yasushi Fukuda, Daichi Fujimoto, Satoru Miura, Keiichi Ota, Yuichi Ozawa, Satoshi Hara, Junko Tanizaki, Koichi Azuma, Shota Omori, Motoko Tachihara, Kazumi Nishino, Akihiro Bessho, Yasutaka Chiba, Koji Haratani, Kazuko Sakai, Kazuto Nishio, Nobuyuki Yamamoto, Kazuhiko Nakagawa

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

Purpose: Although the efficacy of programmed cell death–1 (PD-1) blockade is generally poor for non–small cell lung cancer (NSCLC) with activating mutations of the epidermal growth factor receptor (EGFR) gene, EGFR tyrosine kinase inhibitors (TKIs) may improve the tumor immune microenvironment. We performed a randomized study to assess whether nivolumab improves outcome compared with chemotherapy in such patients previously treated with EGFR-TKIs. Patients and Methods: Patients with EGFR-mutated NSCLC who acquired EGFR-TKI resistance not due to a secondary T790M mutation of EGFR were randomized 1:1 to nivolumab (n = 52) or carboplatin–pemetrexed (n = 50). The primary endpoint was progression-free survival (PFS). Results: Median PFS and 1-year PFS probability were 1.7 months and 9.6% for nivolumab versus 5.6 months and 14.0% for carboplatin–pemetrexed [log-rank P < 001; hazard ratio (HR) of 1.92, with a 60% confidence interval (CI) of 1.61–2.29]. Overall survival was 20.7 and 19.9 months [HR, 0.88 (95% CI, 0.53–1.47)], and response rate was 9.6% and 36.0% for nivolumab and carboplatin–pemetrexed, respectively. No subgroup including patients with a high tumor mutation burden showed a substantially longer PFS with nivolumab than with carboplatin-pemetrexed. The T-cell–inflamed gene expression profile score (0.11 vs. -0.17, P = 0.036) and expression of genes related to cytotoxic T lymphocytes or their recruitment were higher in tumors that showed a benefit from nivolumab. Conclusions: Nivolumab did not confer a longer PFS compared with carboplatin-pemetrexed in the study patients. Gene expression profiling identified some cases with a favorable tumor immune microenvironment that was associated with nivolumab efficacy.

本文言語英語
ページ(範囲)893-902
ページ数10
ジャーナルClinical Cancer Research
28
5
DOI
出版ステータス出版済み - 3月 1 2022

!!!All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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