Journal
CLINICAL CANCER RESEARCH
Volume 28, Issue 5, Pages 893-902Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-21-3194
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Funding
- Ono Pharmaceutical Co. Ltd. (Osaka, Japan)
- Bristol Myers Squibb Co. Ltd. (Tokyo, Japan)
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The study found that nivolumab did not show a longer progression-free survival (PFS) compared to carboplatin-pemetrexed in NSCLC patients with EGFR tyrosine kinase inhibitor resistance. However, gene expression profiling identified some tumors with a favorable immune microenvironment associated with the efficacy of nivolumab.
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-TM 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 1.6-12.29]. 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.
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