JTO clinical and research reports
Dacomitinib With or Without Dose Titration in Treatment-Naive Advanced EGFR-Mutated NSCLC - Primary Analysis of the ATORG-003 Phase 2 Trial
By Tan AC, Kim TM, Zhou S and 11 others.
Abstract
Introduction
Dacomitinib is an approved second-generation EGFR tyrosine kinase inhibitor. In the phase 3 ARCHER 1050 trial, both progression-free survival (PFS) and overall survival (OS) were improved with first-line dacomitinib compared with gefitinib. Post hoc analysis revealed that efficacy (PFS, OS) was similar in both dose-reduced patients and the overall study population. ATORG-003 evaluated a dose-titration strategy to improve tolerability while maintaining efficacy. This is also the first prospective study of dacomitinib's intracranial efficacy and resistance (tissue and plasma next-generation sequencing).
Methods
ATORG-003 (Asian Thoracic Oncology Research Group; five Asian countries) was a single-arm, investigator-initiated phase 2 trial that enrolled patients with treatment-naive stages IIIB to IV EGFR-mutated NSCLC. Patients received dacomitinib 30 mg daily for 4 weeks, with a shared investigator and patient decision for titration to 45 mg in patients with grade less than or equal to 1 toxicity (Common Terminology Criteria for Adverse Events version 5.0). The primary end point was the 12-month PFS rate (in patients without central nervous system metastases only) compared with the historical control. Secondary end points were time to treatment failure (TTF), objective response rate (ORR), OS, intracranial ORR (iORR) and intracranial PFS (iPFS), and safety and tolerability.