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Published on: August 11, 2017
Effectiveness of EGFR-TKI rechallenge immediately after PD-1 blockade failure
Kyoichi Kaira1, Kunihiko Kobayashi1, Ayako Shiono1
1Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Saitama, Japan.
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.
Insights
Sequential treatment with programmed death-1 (PD-1) blockade followed by epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) rechallenge shows promise for non-small cell lung cancer (NSCLC) patients resistant to EGFR-TKIs. This approach significantly improved response rates and survival outcomes in a retrospective analysis.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Targeted Therapy
Background:
- Limited effective therapies exist for non-small cell lung cancer (NSCLC) patients developing resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).
- Sequential treatment strategies are being explored to overcome acquired resistance in NSCLC.
Purpose of the Study:
- To evaluate the efficacy of programmed death-1 (PD-1) blockade followed by EGFR-TKI rechallenge in NSCLC patients with acquired resistance to EGFR-TKIs.
- To compare outcomes of EGFR-TKI rechallenge after PD-1 blockade versus standard EGFR-TKI rechallenge.
Main Methods:
- Retrospective analysis of 75 advanced NSCLC patients with EGFR mutations previously treated with EGFR-TKIs.
- Comparison of an experimental group (PD-1 blockade followed by EGFR-TKI rechallenge) with a control group (EGFR-TKI rechallenge without prior PD-1 blockade).
- Collection of blood samples to assess lymphocyte percentages before therapy initiation and at EGFR-TKI rechallenge.
Main Results:
- Objective response rates for EGFR-TKI rechallenge were significantly higher in the experimental group (46.1%) compared to the control group (16.1%) (p=0.026).
- Median progression-free survival (PFS) and overall survival (OS) after EGFR-TKI rechallenge were 5.0 and 25.0 months, respectively, in the experimental group.
- Sequential PD-1 blockade and EGFR-TKI rechallenge was repeated up to three times in some patients, yielding partial responses without increased toxicity.
Conclusions:
- EGFR-TKI rechallenge immediately after PD-1 blockade is an effective therapeutic strategy for NSCLC patients who have developed resistance to EGFR-TKIs.
- This sequential treatment approach offers a viable option for managing acquired resistance in EGFR-mutated NSCLC.
- Further prospective studies are warranted to confirm these findings and optimize treatment sequencing.
