Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer
Corral J (1), Mok TS (2), Nakagawa K (3), Rosell R (4), Lee KH (5), Migliorino MR (6), Pluzanski A (7), Linke R (8), Devgan G (9), Tan W (10), Quinn S (11), Wang T (12), Wu YL (13).
We evaluated reasons for dacomitinib dose reduction (DR) and examined adverse event (AE) incidence, key efficacy end points (progression-free survival [PFS]/overall survival [OS]), and pharmacokinetics in dose-reducing patients in the ARCHER 1050 trial.
Patients & methods:
Newly diagnosed patients with EGFR mutation-positive, advanced non-small-cell lung cancer received oral dacomitinib (45 mg once-daily [QD]), with stepwise toxicity-managing DR (30 and 15 mg QD) permitted.
Skin toxicities (62.7%) were the most common DR-leading AEs. The AE incidence and severity decreased following DRs. Initial plasma dacomitinib exposure (45 mg QD) was generally lower in patients remaining at 45 mg QD compared with dose-reducing patients. Median PFS and OS were similar in all dacomitinib-treated patients and dose-reducing patients.
Tolerability-guided dose modifications enabled patients to continue with dacomitinib and benefit from PFS/OS improvement.