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Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint
Qian Chen1, Xiaoling Shang1, Ni Liu1
1Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan, China.
Background:
Although immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.
Methods:
The profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.
Results:
Patients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (<1%) PD-L1 expression than with positive (≥1%) PD-L1 expression (15.61 vs. 7.40 months, p = 0.138). Median PFS and OS were significantly shorter in heavily treated patients (prior lines of therapy ≥3 lines vs. <3 lines: mPFS, 1.80 vs. 2.50 months, p = 0.003; mOS, 6.70 vs. 14.00 months, p = 0.031). ORR was also lower in patients who had received ≥3 prior lines of therapy compared to in those <3 prior lines of therapy (0.00% vs. 21.67%, p = 0.002).
Conclusion:
Patients with major EGFR mutations showed poorer responses to ICIs than those with rare EGFR mutations. EGFR-mutated patients with lower PD-L1 expression showed a trend towards a longer OS after receiving ICIs. ICIs should be administered as early as possible to previously treated EGFR-mutated NSCLC patients. ICI-based combined therapies may be a direction for treatment of these patient subtypes in the future.
Insights
Immune checkpoint inhibitors (ICIs) show limited efficacy in non-small cell lung cancer (NSCLC) with EGFR mutations. Rare EGFR mutations and early ICI treatment are associated with better outcomes, suggesting new therapeutic strategies.
Area of Science:
- Oncology
- Immunotherapy
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) exhibit limited efficacy in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.
- However, a subset of these patients demonstrates response to ICIs, necessitating identification of predictive features.
Purpose of the Study:
- To identify patient characteristics associated with better response to ICIs in advanced NSCLC with EGFR mutations.
- To explore optimal treatment strategies for this patient population.
Main Methods:
- Retrospective review of 114 advanced NSCLC patients with EGFR mutations treated with ICIs.
- Analysis of EGFR subtypes, PD-L1 expression, and prior treatment lines' impact on ICI efficacy.
Main Results:
- Patients with major EGFR mutations (L858R, 19Del) had shorter progression-free survival (PFS) and lower objective response rates (ORR) compared to rare mutations.
- Heavily pre-treated patients (≥3 lines) showed significantly shorter PFS and overall survival (OS) and lower ORR.
- A trend towards longer OS was observed in patients with negative PD-L1 expression (<1%).
Conclusions:
- Major EGFR mutations are associated with poorer ICI response.
- Early administration of ICIs in previously treated EGFR-mutated NSCLC patients is recommended.
- ICI-based combination therapies represent a promising future direction.
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