Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer

Abstract

Background: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) leads to initial response in most patients with EGFR-mutated non-small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation of patients with NSCLC with EGFR mutations who exhibit clinical outcomes that require treatment with immune checkpoint inhibitors (ICIs). Therefore, to identify eligible cases to treat with ICIs, we retrospectively analyzed the correlation between clinical features and the efficacy of ICIs in patients with EGFR mutations.

Patients and methods: We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who were treated with ICIs after developing resistance to EGFR-TKIs between February 2016 and April 2018 at 6 institutions in Japan. The association between clinical outcomes and the efficacy of ICIs was investigated.

Results: We enrolled 27 patients who harbored EGFR-activating mutations. The objective response and disease control rates were higher in patients with uncommon EGFR mutations than in those with common EGFR mutations (71% vs 35.7% and 57% vs 7%, P = 0.14 and P < 0.01, respectively). Patients with uncommon EGFR mutations or without T790M mutations exhibited a significantly longer median progression-free survival than those with common EGFR mutations or with T790M mutations (P = 0.003 and P = 0.03, respectively).

Conclusion: Patients with uncommon EGFR mutations and without T790M mutations are associated with the best outcomes for treatment with immunotherapy among those with EGFR-mutated NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders with EGFR mutations.

Keywords: EGFR mutation; biomarker; immunology; non-small cell lung cancer.

Figure 1

Frequency of best overall response to immune checkpoint inhibitors (ICIs) after acquired resistance to EGFR‐TKI treatment in patients with EGFR‐mutated NSCLC. Frequency of best overall response to ICIs for all patients (N = 27) (A), patients with common EGFR mutations (N = 20) (B), and patients with uncommon EGFR mutations (N = 7) (C) are shown in the pie chart. ICI, immune checkpoint inhibitor; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; NSCLC, non‐small cell lung cancer

Figure 2

Kaplan‐Meier curves for PFS and TTF in patients with EGFR‐mutated NSCLC treated with immune checkpoint inhibitors after acquired resistance to EGFR‐TKI treatment. (A, B) PFS (A) and TTF (B) curves for all patients (N = 27), and (C, D) PFS (C) and TTF (D) curves for patients with common (N = 20) and uncommon (N = 7) EGFR mutations. (E, F) PFS (E) and TTF (F) curves for patients with T790M‐positive (N = 7) and T790M‐negative (N = 17) EGFR mutations. Column signs denote censoring. PFS, progression‐free survival; TTF, time to treatment failure; EGFR, epidermal growth factor receptor; TKI, tyrosine kinase inhibitor; NSCLC, non‐small cell lung cancer

Figure 3

Kaplan–Meier curves for progression‐free survival (PFS) and time to treatment failure (TTF) following treatment with immune checkpoint inhibitors according to EGFR mutation status and/or acquired T790M mutations in patients with EGFR‐mutated NSCLC. (A, B) PFS (A) and TTF (B) curves for uncommon EGFR mutation plus T790M‐positive (red line), common EGFR mutation plus T790M ‐positive (green line), and common EGFR mutation plus T790M‐negative (blue line) (N = 27) NSCLC. Column signs denote censoring. PFS, progression‐free survival; TTF, time to treatment failure; EGFR, epidermal growth factor receptor; NSCLC, non‐small cell lung cancer