Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint inhibitors

Abstract

BackgroundAlthough 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.MethodsThe 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.ResultsPatients 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).ConclusionPatients 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.

An open label, safety study of Asian patients with advanced non-small-cell lung cancer receiving second-line nivolumab monotherapy (CheckMate 870)

“… 33 Recent evidence suggests that immune checkpoint inhibitors may provide clinical benefit regardless of EGFR/ALK mutation status in certain patients. 34 – 36 In this study, 63% and 49% of EGFR-positive patients, and 60% and 40% of ALK-positive patients, were alive at 1 and 2 years, respectively. Moreover, 1- and 2-year survival rates were 71% and 43%, respectively, in B-RAF -positive patients.…”

“…Based on evidence available to date, Chen and colleagues proposed that in EGFR positive patients with TKI-resistant disease who have a low number of previous treatments, immune checkpoint inhibitor therapy may be a preferred treatment option in the future. 35 Additional data from future clinical trials is required to confirm the potential role of immune checkpoint inhibitors in the treatment of patients with EGFR -positive NSCLC.…”

Overexpression of TWF1 promotes lung adenocarcinoma progression and is associated with poor prognosis in cancer patients through the MMP1 signaling pathway

“…Epidermal growth factor receptor (EGFR) mutation is one of the driver mutations for LUAD ( 13 , 15 ). Multiple EGFR-targeted tyrosine kinase inhibitors (TKIs; e.g., gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) have been determined as standard initial treatment for patients harboring EGFR mutations, which has saved numerous patients with mid-/late-stage cancers ( 15 , 16 ). However, EGFR mutations can only be detected in about 50% of Asian and 10% of Eastern patients ( 16 ).…”

“…Multiple EGFR-targeted tyrosine kinase inhibitors (TKIs; e.g., gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib) have been determined as standard initial treatment for patients harboring EGFR mutations, which has saved numerous patients with mid-/late-stage cancers ( 15 , 16 ). However, EGFR mutations can only be detected in about 50% of Asian and 10% of Eastern patients ( 16 ). Therefore, searching for more effective targets for LUAD treatment is of great significance.…”

Sintilimab plus anlotinib as second‐ or third‐line therapy in metastatic non‐small cell lung cancer with uncommon epidermal growth factor receptor mutations: A prospective, single‐arm, phase II trial

“…Immune checkpoint inhibitors (ICIs) targeting the programmed death 1 (PD‐1)/PD ligand 1 (PD‐L1) pathway have revolutionized the treatment of advanced NSCLC; however, the observed OS benefit with second‐line ICI monotherapy over docetaxel in patients with NSCLC has failed to extend to EGFR ‐mutated patients 17,18 . Retrospective studies have suggested that some EGFR mutation subtypes may be associated with sensitivity to ICIs; specifically, patients with ex20ins or G719X appear to achieve a longer PFS and a higher ORR than patients with classic EGFR mutations 19,20 …”