Sensitivity to Immune Checkpoint Blockade in Advanced Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations

Abstract

Besides platinum-based chemotherapy, no established treatment option exists for advanced non-small-cell lung cancer (NSCLC) patients with <i>EGFR</i> exon 20 (Ex20ins) insertion mutations. We sought to determine the clinical outcome of patients with this <i>EGFR</i> mutation subtype in the immunotherapy era. Thirty NSCLCs with <i>EGFR</i> Ex20ins mutations were identified, of whom 15 had received immune checkpoint blockade (ICB) treatment as monotherapy (N = 12), in combination with chemotherapy (N = 2) or with another immunotherapeutic agent (N = 1). The response rate was observed in 1 out of 15 patients (6.7%), median progression-free survival (PFS) was 2.0 months and median overall survival (OS) was 5.3 months. A trend towards an inferior outcome in terms of PFS and OS was observed for patients receiving ICB treatment in the first versus second line setting (PFS: 1.6 months versus 2.7 months, respectively, <i>p</i> = 0.16-OS: 2.0 months versus 8.1 months, respectively, <i>p</i> = 0.09). Median OS from the time of diagnosis of advanced disease was shorter for patients treated with ICB versus those who did not receive immunotherapy (12.9 months versus 25.2 months, respectively, <i>p</i> = 0.08), which difference remained associated with a worse survival outcome at multivariate analysis (<i>p</i> = 0.04). Treatment with ICB is poorly effective in NSCLCs with <i>EGFR</i> Ex20ins mutations, especially when given in the first-line setting. This information is crucial in order to select the optimal treatment strategy for patients with this subtype of <i>EGFR</i> mutation.