Pembrolizumab in Combination with Chemotherapy in Patients with ERBB2-Mutated Non-Small Cell Lung Cancer

BackgroundHuman epidermal growth factor receptor 2 (ERBB2) mutation is a known oncogenic driver mutation in a small proportion of non-small cell lung cancers (NSCLCs). Many targeted therapies are being developed and investigated for the treatment of ERBB2-mutated NSCLC, however none of these agents have yet been approved as a front-line treatment. Thus, platinum-based chemotherapy with or without immunotherapy remains the preferred first-line therapy for ERBB2-mutated NSCLC.ObjectiveWe aimed to study the activity of chemotherapy in combination with pembrolizumab as first-line treatment in patients with stage IV ERBB2-mutated NSCLC.Patients and MethodsWe retrospectively identified five patients with ERBB2-mutated NSCLC treated with carboplatin, pemetrexed and pembrolizumab as first-line therapy between 2018 and 2020. Overall survival (OS), progression-free survival (PFS), and time to next therapy (TTNT) were summarized by Kaplan–Meier methodology using R 4.0.5 with median time to event. Response rates defined by partial response (PR) or PR + stable disease (SD) and 95% Clopper–Pearson confidence interval (CI) were calculated.ResultsThe median age of these five patients was 60 years and all five patients’ tumors had ERBB2 mutations—4 had exon 20 mutation and 1 had exon 23 mutation. With a median follow-up of 32 months, the median OS was 24 months, the median PFS was 9 months, and the median TTNT was 9 months. The response rate was 0.6 for PR (Clopper–Pearson exact 95% CI 0.147–0.947) and 0.8 for PR and SD (Clopper–Pearson exact 95% CI 0.284–0.995). No unexpected toxicities were observed.ConclusionIn a small number of patients, chemotherapy and pembrolizumab as first-line therapy in ERBB2-mutated NSCLC patients demonstrated activity similar to previous reports with this regimen. Future clinical trials are needed to determine the role of chemotherapy and immunotherapy for this patient population in the context of emerging targeted agents.