Dacomitinib as a First-Line Therapy for Advanced EGFR-Mutated Non-Small Cell Lung Cancer Without Brain Metastases: A Multicenter Retrospective Observational Study.

[BACKGROUND] Real-world evidence regarding the use of dacomitinib as a first-line therapy for advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations remains limited. This multicenter, retrospective cohort study aimed to evaluate the clinical outcomes of dacomitinib as a first-line treatment in patients with untreated advanced EGFR-mutant NSCLC without brain metastases.

[PATIENTS AND METHODS] This retrospective analysis included 161 patients with stage IIIB/IV EGFR-mutant NSCLC without brain metastasis at baseline who received first-line dacomitinib between October 2020 and August 2023 at four Taiwanese cancer centers. The primary outcomes included the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), predictive risk factors for PFS, and adverse events (AEs).

[RESULTS] The ORR was 64.0%, and the disease control rate (DCR) reached 91.3%. The median PFS was 20.93 months (95% CI: 17.55-24.32), and the median OS was 41.27 months (95% CI: 31.71-50.82). Multivariate analysis revealed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2, bone metastasis, and liver metastasis were independent predictors of shorter PFS. Among patients who experienced disease progression and underwent rebiopsy, the secondary T790M mutation rate was 50.6%. Most treatment-related AEs were grade 1-2 and manageable.

[CONCLUSIONS] Dacomitinib demonstrated favorable efficacy and tolerability as a first-line therapy in advanced NSCLC patients with common EGFR mutations (exon 19 deletion or L858R). A baseline ECOG PS ≥ 2 and the presence of bone or liver metastases were significantly associated with worse PFS, suggesting a need for additional therapeutic strategies in these subgroups.