背景:在阿霉素中加入曲贝替丁,其次是trabectedin维护,作为晚期平滑肌肉瘤患者的一线治疗,可能比单独使用阿霉素具有更好的疗效。
方法:我们进行了一项3期试验,纳入之前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单药阿霉素(六个周期)或阿霉素加曲贝替丁(六个周期),在阿霉素-曲贝替丁组没有疾病进展的患者中,继续使用曲贝替丁作为维持治疗。六个周期的治疗后,每组均允许手术切除残留病。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(子宫与软组织)和疾病阶段(局部晚期与转移性)。先前报告了主要终点结果。
结果:共有150名患者接受了随机分组。在中位随访55个月时(四分位数间距,49至63),共有107例患者死亡(阿霉素-曲贝替丁组47例,阿霉素组60例).阿霉素-曲贝替丁组的中位总生存期更长(33个月;95%置信区间[CI],阿霉素组(24个月;95%CI,19至31)为26至48);调整后的死亡风险比为0.65(95%CI,0.44至0.95)。在与早期报告一致的发现中,阿霉素-曲贝替丁组(12个月;95%CI,10~16)的无进展生存期长于阿霉素组(6个月;95%CI,4~7);调整后的进展或死亡风险比为0.37(95%CI,0.26~0.53).阿霉素加曲贝替丁的不良事件发生率和剂量减少的患者百分比高于单独使用阿霉素。
结论:多柔比星和曲贝替丁诱导联合治疗,其次是trabectedin维护,与总生存期和无进展生存期的改善有关,与单独的阿霉素相比,转移性或手术不可切除的子宫或软组织平滑肌肉瘤患者。(由PharmaMar等资助;LMS04ClinicalTrials.gov编号,NCT02997358。).
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.).