A phase II trial of trabectedin (T) in patients (pts) with HER2-positive and BRCA1/2 germ-line-mutated metastatic breast cancer (MBC).

1038 Background: Single agent T has shown activity in soft tissue sarcoma (STS), ovarian, and breast carcinoma. The European Commission has approved T for STS treatment in adults after failure of standard therapy and for platinum sensitive relapsed ovarian cancer. In 3 phase II studies T showed antitumor activity in pts with pretreated MBC. Preclinical and clinical data suggested T may display specific activity among certain nucleotide excision repair (NER) intact or homologous recombination repair (HRR) deficient MBC, and prompted this phase II trial. Methods: T was given at 1.3 mg/m2 as a 3-hour iv infusion 3qwks to pts with pretreated progressive MBC: Group A: ER/PR/HER2- negative; Group B: HER2 overexpressed (3+), and Group C: BRCA1/2 mutation carriers. Endpoints were objective response rate by RECIST, duration of response, progression free survival (PFS), safety, and pharmacogenomics (PGx). Results: Group A was closed due to low response rate; results have already been presented. A total of 55 pts ha...