Presentado Sabado dia 5 Mayo :A phase II trial of trabectedin (T) in patients (pts) with HER2-positive and BRCA1/2 germ-line-mutated metastatic breast cancer (MBC).
ABSTRACT Nº 1038 .
Author(s): K. L. Tedesco, J. L. Blum, A. Goncalves, J. Lubinski, N. Ben-Baruch, C. R. Osborne, P. Lardelli, J. C. Tercero, F. A. Holmes, S. Delaloge; US Oncology, New York Oncology Hematology, Albany, NY; Baylor-Charles A. Sammons Cancer Center, Texas Oncology PA, and US Oncology, Dallas, TX; Institut Paoli Calmettes, Marseille, France; International Hereditary Cancer Center, Szczecin, Poland; Kaplan Medical Center, Rehovot, Israel; PharmaMar, Colmenar Viejo, Madrid, Spain; US Oncology Research, Houston, TX; Institut Gustave Roussy, Villejuif, France
Abstract:
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 have been enrolled in groups B (31) and C (24) (median [med] age: 53, ECOG 0/1: 25/30); med number of prior chemotherapy lines: 3 (1-8). Med number of T cycles administered: 3 (1-12+) for both groups. Per external review, of 29 evaluable HER2 3+ pts, 3 confirmed partial responses (PR) were observed. From 21 BRCA1/2 mutation carrier pts, there were 3 confirmed PR. 17 (58.6%) and 8 (38.1%) pts in groups B and C achieved stable disease (SD). Two HER2 3+ pts had SD longer than 6 months. Med PFS was 3.9 months in each arm. The most frequent grade 3-4 laboratory disorders were neutropenia (38%) and (57%), and ALT elevations (57%) and (45%) for groups B and C, respectively. Fatigue, nausea, and vomiting were the most common AEs (51%, 39% and 20% for both groups B and C) of mild to moderate severity in the vast majority of pts. Tissue samples from HER2 3+ pts and BRCA mutation carriers were collected for RNA expression analysis (XPG + ERCC1 + BRCA1). Analyses are ongoing.
Conclusions: T showed anti-MBC activity in BRCA1/2 mutation carriers and HER2 3+ pts with a manageable safety profile. Complete efficacy data from groups B and C and PGx results will be discussed to help selecting the MBC patients who are at highest chance for response.