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

## TL;DR

This study evaluates dacomitinib as a first-line treatment for advanced EGFR-mutated lung cancer without brain metastases, finding it effective with manageable side effects.

## Contribution

Provides real-world evidence on dacomitinib's efficacy and identifies risk factors for shorter progression-free survival in EGFR-mutated NSCLC patients.

## Key findings

- Dacomitinib achieved a 64% objective response rate and 91.3% disease control rate in EGFR-mutated NSCLC patients.
- Median progression-free survival was 20.93 months and median overall survival was 41.27 months with dacomitinib treatment.
- ECOG performance status ≥2, bone metastasis, and liver metastasis were independent predictors of shorter progression-free survival.

## Abstract

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.

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).

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.

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.