Efficacy analysis of immunotherapy‑based combinations for patients with EGFR‑mutant advanced non‑small cell lung cancer after TKI failure
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Meifang Li1, Cheng Lin2, Jinghui Lin1
1Department of Thoracic Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian 350014, P.R. China.
Abstract:
Treatment options for epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) following tyrosine kinase inhibitor (TKI) failure are limited, and platinum-based chemotherapy remains the main treatment. The development of effective immunotherapy for this disease has been challenging. In the present study, 37 patients with EGFR-mutant advanced NSCLC who were treated with programmed cell death-1 (PD-1) inhibitor-based combinations after TKI failure were reviewed. The total cohort had a median progression-free survival (mPFS) of 5.2 months (95% CI, 4.077-6.323 months) and a median overall survival (mOS) of 18.3 months (95% CI, 12.932-23.668 months). Patients with Eastern Cooperative Oncology Group performance-status (ECOG-PS) scores of 0 or 1 had longer mPFS than those with ECOG-PS scores of 2 (5.4 vs. 2.4 months; P=0.006). In addition, a PFS benefit was observed in patients with EGFR T790M-negative compared with EGFR T790M-positive tumors (mPFS 6.2 vs. 4.4 months; P=0.041). Patients treated with immunotherapy-based combinations as a front-line therapy had a longer mPFS than those in which the combinations were used as a late-line therapy (6.2 vs. 2.4 months; P<0.001). PD-1 inhibitor combined with chemotherapy and bevacizumab did not show a clear advantage over PD-1 inhibitor combined with chemotherapy alone (mPFS, 6.2 vs. 4.4 months; P=0.681), although it resulted in an improved overall response rate (ORR) and disease control rate. Notably, the 7 patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score of ≥50% had an ORR of 100% and an mPFS of 8.3 months. Therefore, it is suggested that PD-1 inhibitor-based combinations should be a priority treatment option in selective populations, such as those with low ECOG-PS scores, T790M-negative status or high PD-L1 expression in EGFR-mutant NSCLC after TKI failure. The use of immunotherapy and chemotherapy in combination with antiangiogenic agents appears to be a promising combination therapy for such patients.
Insights
Programmed cell death-1 (PD-1) inhibitor combinations show promise for advanced EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) failure. These treatments offer improved progression-free survival in specific patient groups, including those with low ECOG-PS scores or high PD-L1 expression.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Treatment for advanced EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) failure is limited.
- Platinum-based chemotherapy is a standard treatment, but effective immunotherapy options are needed.
Purpose of the Study:
- To review the efficacy of programmed cell death-1 (PD-1) inhibitor-based combinations in patients with EGFR-mutant advanced NSCLC post-TKI failure.
- To identify patient subgroups that may benefit most from these combination therapies.
Main Methods:
- Retrospective review of 37 patients with EGFR-mutant advanced NSCLC treated with PD-1 inhibitor-based combinations after TKI failure.
- Analysis of progression-free survival (PFS), overall survival (OS), and overall response rate (ORR).
- Subgroup analyses based on ECOG performance status (ECOG-PS), EGFR T790M mutation status, and PD-L1 expression.
Main Results:
- Median PFS was 5.2 months and median OS was 18.3 months for the total cohort.
- Patients with ECOG-PS 0-1, EGFR T790M-negative tumors, and those receiving immunotherapy as first-line therapy showed significantly longer PFS.
- High PD-L1 expression (≥50%) correlated with a 100% ORR and 8.3 months mPFS.
- PD-1 inhibitor plus chemotherapy and bevacizumab did not significantly improve PFS over PD-1 inhibitor plus chemotherapy alone.
Conclusions:
- PD-1 inhibitor-based combinations are a viable treatment option for select EGFR-mutant NSCLC patients post-TKI failure.
- Priority treatment should be considered for patients with low ECOG-PS, T790M-negative status, or high PD-L1 expression.
- Combination therapy with immunotherapy, chemotherapy, and antiangiogenic agents shows promise.
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