• Patricia Pautier, Antoine Italiano, Sophie Piperno-Neumann, Christine Chevreau, Nicolas Penel, Nelly Firmin, Pascaline Boudou-Rouquette, François Bertucci, Valérie Lebrun-Ly, Isabelle Ray-Coquard, Elsa Kalbacher, Emmanuelle Bompas, Olivier Collard, Nicolas Isambert, Cécile Guillemet, Maria Rios, Axel Le Cesne, Corinne Balleyguier, Baptiste Archambaud, Florence Duffaud, and French Sarcoma Group.
• From the Departments of Medical Oncology (P.P., A.L.C.), Radiology (C.B.), and Biostatistics and Epidemiology (B.A.), Institut Gustave-Roussy, and Oncostat, INSERM Unité 1018, Labeled Ligue Contre le Cancer (B.A.), Villejuif, the Department of Medical Oncology, Institut Bergonié, and the Faculty of Medicine, University of Bordeaux, Bordeaux (A.I.), the Department of Medical Oncology, Institut Curie (S.P.-N.), and the Department of Medical Oncology, Hôpital Cochin-Port Royal (P.B.-R.), Paris, the Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse (C.C.), Lille University, and the Department of Medical Oncology, Centre Oscar Lambret, Lille (N.P.), the Department of Medical Oncology, Institut Régional du Cancer, INSERM Unité 1194, Institut de Recherche en Cancérologie de Montpellier, and the University of Montpellier, Montpellier (N.F.), the Department of Medical Oncology, Institut Paoli-Calmettes (F.B.), the Department of Medical Oncology, La Timone University Hospital (F.D.), and Aix-Marseille Université (F.B., F.D.), Marseille, the Department of Medical Oncology, Centre Hospitalo-Universitaire Dupuytren, Limoges (V.L.-L.), the Department of Medical Oncology, Centre Léon Bérard, and University Claude-Bernard Lyon 1, Lyon (I.R.-C.), the Department of Medical Oncology, Centre Hospitalier Universitaire de Besançon-Hôpital Jean-Minjoz, Besançon (E.K.), Institut de Cancérologie de l'Ouest, Angers-Nantes (E.B.), Institut de Cancérologie de la Loire, Saint-Priest-en-Jarez (O.C.), Centre Georges-François Leclerc, Dijon (N.I.), the Department of Medical Oncology, Centre Paul Papin, Rouen (C.G.), and Institut de Cancérologie de Lorraine, Vandoeuvre-lès-Nancy (M.R.) - all in France.
• N. Engl. J. Med. 2024 Sep 5; 391 (9): 789799789-799.

BackgroundThe addition of trabectedin to doxorubicin, followed by trabectedin maintenance, may have superior efficacy to doxorubicin alone as first-line treatment in patients with advanced leiomyosarcoma.MethodsWe conducted a phase 3 trial involving patients with metastatic or unresectable leiomyosarcoma who had not received chemotherapy previously. Patients were randomly assigned to receive either single-agent doxorubicin (six cycles) or doxorubicin plus trabectedin (six cycles), with continued trabectedin as maintenance therapy in patients in the doxorubicin-trabectedin group who did not have disease progression. Surgery to resect residual disease was allowed in each group after six cycles of therapy. Analyses of progression-free survival (primary end point) and overall survival (secondary end point) were adjusted for two stratification factors: tumor origin site (uterine vs. soft tissue) and disease stage (locally advanced vs. metastatic). The primary end-point results were reported previously.ResultsA total of 150 patients underwent randomization. At a median follow-up of 55 months (interquartile range, 49 to 63), a total of 107 patients had died (47 in the doxorubicin-trabectedin group and 60 in the doxorubicin group). The median overall survival was longer in the doxorubicin-trabectedin group (33 months; 95% confidence interval [CI], 26 to 48) than in the doxorubicin group (24 months; 95% CI, 19 to 31); the adjusted hazard ratio for death was 0.65 (95% CI, 0.44 to 0.95). In a finding consistent with earlier reports, progression-free survival was longer in the doxorubicin-trabectedin group (12 months; 95% CI, 10 to 16) than in the doxorubicin group (6 months; 95% CI, 4 to 7); the adjusted hazard ratio for progression or death was 0.37 (95% CI, 0.26 to 0.53). The incidence of adverse events and the percentage of patients with dose reductions were higher with doxorubicin plus trabectedin than with doxorubicin alone.ConclusionsCombination therapy with doxorubicin and trabectedin induction, followed by trabectedin maintenance, was associated with improved overall survival and progression-free survival, as compared with doxorubicin alone, among patients with metastatic or surgically unresectable uterine or soft-tissue leiomyosarcoma. (Funded by PharmaMar and others; LMS04 ClinicalTrials.gov number, NCT02997358.).Copyright © 2024 Massachusetts Medical Society.

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