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625 Background: Trabectedin (Yondelis, ET-743) is a marine-derived compound binding the minor groove of DNA that is active at nM concentrations. Trabectedin is thought to act through the transcription-coupled nucleotide excision repair system. In clinical trials Trabectedin has demonstrated activity in soft tissue sarcoma, ovarian and breast cancer. Methods: Patients (pts) with advanced breast cancer exposed to both anthracyclines and taxanes and at most two prior lines of chemotherapy, were randomized in a multicenter Phase II study, to receive Trabectedin on either, 0.58 mg/m2 weekly/three out of four weeks (weekly Arm) or 1.3mg/m2 every 3 weeks schedule (q3weeks Arm). Pts were premedicated with Dexamethasone. Results: Both Arms were well balanced for performance status and prior anticancer therapy (median=4). Pts (weekly vs. q3weeks) received a median of 2 vs 4 cycles, respectively; RDI delivered was 76 vs. 81%. Efficacy: Responses were 1/27 vs 3/25, including one CR, for a RR of 3.75 vs 12%. TTP (hazard ratio =1.5/ p-value=0.18) and OS, showed a superiority trend for the q3weekly schedule. Safety: 201 cycles were delivered. Most notable grade 3/4 lab abnormalities (weekly vs q3weeks) were neutropenia, 0% vs 9% and ALT, 8% vs 18%. However, when the drug was discontinued because of an adverse event (19% in the weekly Arm, compared to only 4% in the q3weeks Arm) this was always due to liver related lab abnormalities. Six cases of mild CPK elevations were observed, all on the weekly Arm. Asthenia and nausea/vomiting were equally common on both Arms (66% vs 54% and 55% vs 45%). Conclusion: Activity was noted in both Arms of this heavily pretreated patient population. A consistent trend towards superior efficacy was noted in the q3weekly Arm. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Pharmaceutical Research and Development Johnson & Johnson Pharmaceutical Research and Development
Gurtler et al. (Wed,) studied this question.