Efficacy and safety of dacomitinib in advanced non-small cell lung cancer patients harboring uncommon EGFR mutations: Real-world evidence from China.

Abstract

e21163 Background: Dacomitinib has been approved for advanced non-small cell lung cancer (NSCLC) patients harboring common epidermal growth factor receptor ( EGFR) alterations; however, clinical evidence on its activity to uncommon EGFR mutations is currently limited. Methods: Patients were collected from the Chinese National Cancer Center and the Chinese PLA hospital between July 2017 and December 2021. The objective response rate and disease control rate were determined by RECIST 1.1. Adverse events were assessed by CTCAE 5.0. Kaplan-Meier method was utilized to assess progression-free survival (PFS). Results: In total, 38 advanced NSCLC patients harboring uncommon EGFR mutations treated with dacomitinib in multi-line settings were enrolled. Among these patients, 30 cases carried major uncommon mutations, of which 13 cases harbored G719A/C, 8 carried S768I + G719A/C/S, 7 had L861Q, 2 had L861Q + G719A, and the remaining 8 patients carried non-major uncommon mutations, of which 3 harbored E709X, 3 carried L747P, 1 had H183D, and 1 had G598V. The initial dose of dacomitinib (45 mg, 30 mg, or 15 mg once daily) was based on the performance status and comorbidities of the patient. In the whole cohort, 55.3 % of patients (21/38) had a confirmed partial response and 89.5 % (34/38) had disease control, and the median PFS was 10.3 months (95 % confidence interval [CI], 5.8–14.8). For non-major uncommon mutations, 62.5 % of patients (5/8) had a confirmed partial response and 87.5 % (7/8) had disease control, and the median PFS was 11.5 months (95 % CI, 6.2–16.8). Except for one case not available for brain evaluation, control of the intracranial metastases was observed in 16 patients (16/18, 88.9 %), and the median PFS was 6.6 months (95 % CI, 6.3–6.9). Subgroup analysis did not show a significant difference in PFS between patients with and without major uncommon mutations (HR = 0.786, 95 % CI 0.265-2.331, P = 0.639), but between those with and without brain metastases (HR = 3.350, 95 % CI 1.334-8.411, P = 0.005). No grade 4-5 adverse events (AEs) occurred, but all patients had grade 1–2 AEs, and 13.2 % (5/38) of patients required a dosage reduction due to intolerable AEs. Conclusions: This real-world study indicates that dacomitinib is potent and well-tolerated in NSCLC patients harboring uncommon EGFR mutations in multi-line settings, and has favourable activity for brain metastases.[Table: see text]