Lurbinectedin is active and has a manageable safety profile in patients with relapsed Ewing sarcoma, according to trial results published in Clinical Cancer Research.
The phase 2 trial (ClinicalTrials.gov Identifier: NCT02454972) included 28 evaluable patients with relapsed Ewing sarcoma. The patients’ median age at baseline was 33 years (range, 18-74 years), and 57% were men.
Most patients (58%) had extraosseous Ewing sarcoma, 42% had osseous Ewing sarcoma, and 36% had metastatic disease at 3 or more sites. The most common sites for metastasis were lung, bone, and pleura. All patients received a median of 2 prior lines of systemic therapy (range, 1-5).
Patients received a median of 4 cycles of lurbinectedin (range, 1-14). The median follow-up was 8.3 months.
The overall response rate was 14.3%. Four patients achieved a partial response, 2 with osseous and 2 with extraosseous disease. The median duration of response was 4.2 months.
The clinical benefit rate was 39.3%, and the disease control rate was 57.1%. Clinical benefit was defined as response or disease stabilization for at least 4 months. Disease control was defined as response or disease stabilization for any duration.
The median progression-free survival was 2.7 months, and the median overall survival was 12.0 months.
After stopping treatment with lurbinectedin, 19 patients (67.9%) received subsequent antitumor therapy. The most commonly used drugs were cyclophosphamide, gemcitabine, and ifosfamide. Response to first subsequent therapy was noted in 2 patients (10.5%) who did not respond to lurbinectedin.
The safety profile of lurbinectedin was manageable, according to the researchers. There were no treatment discontinuations or deaths due to toxicity.
The most common grade 3/4 adverse events were neutropenia (57%), leukopenia (46%), anemia (14%, grade 3 only), thrombocytopenia (14%), and treatment-related febrile neutropenia (14%).
Myelosuppression was reversible. It was managed with cycle delays, dose reductions, granulocyte-colony stimulating factor (G-CSF) support, and transfusions. Researchers suggested that primary G-CSF prophylaxis should be given during lurbinectedin treatment.
“Lurbinectedin could represent a valuable addition to therapies currently used in the management of these complex diseases, which constitute a highly unmet medical need,” the researchers wrote.
Lurbinectedin is currently under investigation in combination with irinotecan for the treatment of solid tumors in a phase 1b/2 trial (ClinicalTrials.gov Identifier: NCT02611024).
Disclosures: This research was partially supported by Pharma Mar S.A. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Subbiah V, Braña I, Longhi A, et al. Antitumor activity of lurbinectedin, a selective inhibitor of oncogene transcription, in patients with relapsed Ewing sarcoma: Results of a basket phase II study. Clin Cancer Res. Published online April 29, 2022. doi:10.1158/1078-0432.CCR-22-0696