Tumor control and objective responses: single-center experience with Ecteinascidin-743 (ET-743, Yondelis), an active compound for the treatment of patients with advanced soft tissue and bone sarcomas

9027 Background: ET-743 (Yondelis) is a marine-derived minor-groove binder which interferes with gene activation and nucleotide excision repair, modulates drug-resistance, induces DNA strand breaks, affects the microtubules and blocks the cell cycle in S and G2. The drug is active in a variety of tumors in vitro and in vivo and responses were observed in sarcoma pts in early studies. We performed a retrospective single-center analysis of treatment outcome with ET-743, mainly involving individuals treated in a named-patient compassionate use program. Written informed consent was obtained from all pts. Methods: ET-743 was administered at dosages of 900-1500 μg/m2 as a 24 h iv. infusion q3w. Treatment was continued until progression or excessive toxicity. Results: 89 patients (median age 49 yrs, performance status 0–2) were analyzed. All of them had documented progressive sarcoma at start of treatment. The most common tumor types were leiomyo- (29), lipo- (16) and osteosarcoma (14). Pts had received a median of 2 prior chemotherapy regimens (range, 0–6). Pretreatment included anthracyclins (93%), ifosfamide (74%) and other drugs. 430 cycles were evaluated (median 4.8 per pat., range 1–31). All pts were assessed for toxicity (NCI CTC 2.0), and the most relevant side effects were neutropenia, thrombopenia, anemia, transaminitis, anorexia, asthenia and nausea/vomiting. The most common reasons for dose reductions were thrombopenia, neutropenia, transaminitis and infections. 70% of the patients discontinued ET-743 due to progression. 82 patients were evaluable for response (RECIST): CR 1, PR 5, MR 1, SD (> 6 mo.) 16, SD (2–6 mo.) 16 and PD 43. The objective response rate (CR+PR) was 6.7% and the clinical benefit rate (CR+PR+MR+SD) at 3 and 6 mo. was 41.6 and 23.4%. Responses included pts with lipo-, leiomyo-, osteo- and myogenic sarcoma (lung, liver and abdominal sites). The median duration of response was 9.8 mo (range 2–43). Conclusions: ET-743 induces long-lasting responses and tumor control in a clinically relevant proportion of pretreated progressive sarcoma pts. Further studies in this indication are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaMar PharmaMar