Effectiveness of EGFR-TKI rechallenge immediately after PD-1 blockade failure

Abstract

Background: There is currently insufficient information available on effective therapies that can be administered to patients with non-small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). However, sequential treatment via programmed death-1 (PD-1) blockade followed by EGFR-TKI rechallenge is suggested to improve the therapeutic efficacy in such patients. Methods: A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR-TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR-TKI rechallenge immediately after the failure of PD-1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD-1 inhibitor therapy before EGFR-TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti-PD-1 therapy and at EGFR-TKI rechallenge. Results: The objective response rates of EGFR-TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression-free survival (PFS) and overall survival (OS) after EGFR-TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR-TKIs was observed in patients with partial response (PR) and without PR after EGFR-TKI rechallenge. In particular, the sequential treatment of PD-1 blockade therapy followed by EGFR-TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR-TKI rechallenge consecutively for the third time yielded a PR without increased toxicities. Conclusions: EGFR-TKI rechallenge immediately after PD-1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR-TKIs.