In the French phase III LMS-04 trial reported in The Lancet Oncology, Pautier et al found that the addition of trabectedin to doxorubicin significantly prolonged progression-free survival as first-line treatment for patients with unresectable or metastatic leiomyosarcoma.
In the open-label multicenter trial, 150 patients were randomly assigned between January 2017 and March 2019 to receive doxorubicin at 60 mg/m² plus trabectedin at 1.1 mg/m² every 3 weeks for up to six cycles, followed by trabectedin maintenance at 1.1 mg/m² every 3 weeks until disease progression or for a maximum of 1 year (n = 74) or doxorubicin at 75 mg/m² every 3 weeks for up to six cycles (n = 76). Overall, 45% of patients and 55% of patients in each group had uterine leiomyosarcoma and soft-tissue leiomyosarcoma, respectively, and 90% of all patients had metastatic disease. Surgery for residual disease was allowed in both groups after six cycles of treatment. The primary endpoint was progression-free survival on blinded independent central review.
Median follow-up was 37 months (interquartile range = 31–44 months). Median progression-free survival was 12.2 months (95% confidence interval [CI] = 10.1–15.6 months) in the doxorubicin/trabectedin group vs 6.2 months (95% CI = 4.1–7.1 months) in the control group (adjusted hazard ratio [HR] = 0.41, 95% CI = 0.29–0.58, P < .0001). Rates at 12 and 24 months were 50.7% vs 16.0% and 30.2% vs 5.3%.
Objective responses were observed in 27 patients (36%) in the combination group, including complete response in 3, and in 10 patients (13%, all partial responses) in the control group (P = .0009). Median duration of response was 12.7 months vs 5.6 months (HR = 0.36, 95% CI = 0.17–0.77, P = .0090). Surgery for residual disease was performed in 20% of patients in the combination group vs 8% of the control group.
Grade 3 or 4 adverse events occurred in 96% of patients in the combination group vs 52% of the control group; the most common in the combination group were neutropenia (80% vs 13%), anemia (31% vs 5%), thrombocytopenia (47% vs 0%), and febrile neutropenia (28% vs 9%).
Serious adverse events occurred in 15 patients (20%) in the combination group, most commonly febrile neutropenia (n = 7) and in 9 (12%) in the control group, most commonly febrile neutropenia (n = 3). One treatment-related death was reported, due to cardiac failure in a patient in the control group.
The investigators concluded, “Doxorubicin plus trabectedin in first-line therapy was found to significantly increase progression-free survival in patients with metastatic or unresectable leiomyosarcomas compared with doxorubicin alone, despite a higher but manageable toxicity, and could be considered an option for the first-line treatment of metastatic leiomyosarcomas.”
Patricia Pautier, MD, of Institut Gustave-Roussy, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by PharmaMar. For full disclosures of the study authors, visit thelancet.com.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.