A randomized phase II trial evaluating CYP2D6 genotype-guided tamoxifen dosing in hormone receptor-positive metastatic breast cancer: TARGET-1.

1046Background: Tamoxifen (TAM) is a prodrug that requires metabolic activation by CYP2D6. Genetic polymorphism of CYP2D6 has been speculated to cause suboptimal efficacy of TAM. Methods: In a phase II multicenter open-label randomized controlled study, we enrolled candidates for first-line TAM therapy who had hormone receptor–positive (HR+) metastatic breast cancer. CYP2D6 genotyping was performed using DNA extracted from whole blood at baseline. Patients with heterozygous (wt/V) or homozygous (V/V) variant alleles of decreased or no function were randomly assigned to TAM at regular dose (20 mg/day, RD arm) or increased dose (40 mg/day, ID arm), and patients with homozygous wild-type alleles (wt/wt) received TAM at 20 mg/day. The primary endpoint was 6-month (6M) progression-free survival (PFS) rate. Secondary endpoints included PFS and plasma levels of TAM and its metabolites. Results: From December 2012 to July 2016, 186 Japanese patients were enrolled. Of 184 evaluable patients, 136 carried wt/V or V/...