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):789-799. doi: 10.1056/NEJMoa2403394.
The 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.
We 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.
A 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.
Combination 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.).
与单独使用多柔比星相比，在转移性或不可切除的平滑肌肉瘤患者中，多柔比星联合 trabectedin 序贯 trabectedin 维持治疗可能具有更好的疗效。
我们开展了一项 3 期临床试验，纳入了既往未接受过化疗的转移性或不可切除的平滑肌肉瘤患者。患者被随机分配接受多柔比星单药治疗（6 个周期）或多柔比星联合 trabectedin 治疗（6 个周期），在多柔比星联合 trabectedin 组中，未发生疾病进展的患者继续接受 trabectedin 维持治疗。在每个治疗周期结束后，两组患者均允许进行手术切除残留病灶。无进展生存期（主要终点）和总生存期（次要终点）的分析调整了两个分层因素：肿瘤起源部位（子宫 vs. 软组织）和疾病分期（局部晚期 vs. 转移性）。主要终点结果先前已有报道。
共有 150 名患者接受了随机分组。中位随访 55 个月（四分位距，49 至 63）时，共有 107 名患者死亡（多柔比星联合 trabectedin 组 47 例，多柔比星组 60 例）。多柔比星联合 trabectedin 组的中位总生存期长于多柔比星组（33 个月；95%置信区间，26 至 48）；死亡风险的调整后 HR 为 0.65（95%置信区间，0.44 至 0.95）。与早期报告一致，多柔比星联合 trabectedin 组的无进展生存期长于多柔比星组（12 个月；95%置信区间，10 至 16）；疾病进展或死亡风险的调整后 HR 为 0.37（95%置信区间，0.26 至 0.53）。多柔比星联合 trabectedin 组的不良反应发生率和剂量减少患者比例高于多柔比星组。
与单独使用多柔比星相比，多柔比星联合 trabectedin 诱导治疗，随后使用 trabectedin 维持治疗，可改善转移性或不可切除的子宫或软组织平滑肌肉瘤患者的总生存期和无进展生存期。（由 PharmaMar 等资助；LMS04 ClinicalTrials.gov 编号，NCT02997358.）。
