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A phase II study shows that this selective inhibitor of oncogene transcription has a good safety profile and it is active in the treatment of patients
Ewing sarcoma is the second most common malignant bone tumor among children, adolescents, and young adults with a prognosis that varies depending on primary tumor site, presence of metastases, and tumor size. There is no established treatment for relapsed Ewing sarcoma: patients have a 5-year survival rate of 13% and the development of therapies is challenging due to its rarity. In a new basket phase II study recently published on Clinical Cancer Research, the selective inhibitor of oncogenic transcription lurbinectedin has shown promising results, with antitumor activity and a manageable safety profile.
The trial involved 28 adult patients with confirmed Ewing sarcoma pretreated with ≤2 chemotherapy lines for metastatic/recurrent disease; patients received lurbinectedin as a 1-hour infusion every 3 weeks. Lurbinectedin blocks transcription and induces DNA double-strand breaks, leading to apoptosis. In preclinical models it was shown that lurbinectedin is effective in suppressing the activity of the oncogenic transcription factor EWS-FLI1 and delayed tumor growth in mice bearing Ewing sarcoma xenografts. Results show that the overall response rate was 14.3%, with median duration of response of 4.2 months; median progression-free survival was 2.7 months, clinical benefit rate was 39.3%, and disease control rate was 57.1%. No deaths or discontinuations were due to toxicity and most common grade 3/4 adverse event was neutropenia (57%). «Lurbinectedin could represent a valuable addition to therapies currently used in the management of these complex diseases, which constitute a highly unmet medical need», authors conclude.