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

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)893-902
    Number of pages10
    JournalClinical Cancer Research
    Volume28
    Issue number5
    DOIs
    Publication statusPublished - Mar 1 2022

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

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