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Efficacy analysis of immunotherapy‑based combinations for patients with EGFR‑mutant advanced non‑small cell lung
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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