Department of Urology and Gynecology, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Fondazione G. Pascale Napoli, Naples, Italy.
Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
Oncologist. 2021 Apr;26(4):e658-e668. doi: 10.1002/onco.13630. Epub 2021 Jan 3.
The noninterventional, prospective NIMES-ROC phase IV study (NCT02825420) evaluated trabectedin plus pegylated liposomal doxorubicin (PLD) in real-life clinical practice.
Eligible participants included adults with platinum-sensitive recurrent ovarian cancer (PS-ROC) who had received one or more cycles of trabectedin/PLD before inclusion according to the marketing authorization. The primary endpoint was progression-free survival (PFS) according to investigator criteria.
Two hundred eighteen patients from five European countries were evaluated, 72.5% of whom were pretreated with at least two prior chemotherapy lines and received a median of six cycles of trabectedin/PLD (range: 1-24). Median PFS was 9.46 months (95% confidence interval [CI], 7.9-10.9), and median overall survival (OS) was 23.56 months (95% CI, 18.1-34.1). Patients not pretreated with an antiangiogenic drug obtained larger median PFS (p < .007) and OS (p < .048), largely owning to differences between the two populations. Twenty-four patients (11.0%) had a complete response, and 57 patients (26.1%) achieved a partial response for an objective response rate (ORR) of 37.2%. Fifty-nine patients (27.1%) had disease stabilization for a disease control rate of 64.2%. No statistically significant difference in PFS, OS, or ORR was observed by BRCA1/2 status and platinum sensitivity. Most common grade 3/4 adverse events (AEs) were neutropenia (30.3%), anemia (6.4%), thrombocytopenia (5.5%), and asthenia (5.0%). No deaths attributed to treatment-related AEs or unexpected AEs occurred.
The combination of trabectedin/PLD represents a clinically meaningful and safe option for patients with PS-ROC regardless of prior treatment with an antiangiogenic drug, being comparable with previously observed outcomes in selected and less pretreated patients from clinical trials.
This noninterventional, prospective study, conducted in 57 reference sites across Europe, consistently confirmed that trabectedin plus pegylated liposomal doxorubicin (PLD) in routine clinical practice represents a clinically meaningful and safe option for women with platinum-sensitive recurrent ovarian cancer. Although the study population represented a heterogeneous, older, and more pretreated population than those in prospective clinical trials, the combination of trabectedin plus PLD induced comparable clinical benefits, with a similar and manageable safety profile. Overall, these findings show that trabectedin in combination with PLD maintains antitumor activity when administered to heavily pretreated patients in real-life clinical practice.
非干预性、前瞻性的 NIMES-ROC Ⅳ期研究（NCT02825420）评估了在真实临床实践中多柔比星脂质体与 trabectedin 的联合应用。
符合条件的参与者包括接受过铂类敏感复发性卵巢癌（PS-ROC）治疗的成年人，在纳入研究前根据药品上市许可已接受过一或多周期 trabectedin/PLD 治疗。主要终点为研究者评估的无进展生存期（PFS）。
来自欧洲五个国家的 218 名患者接受了评估，其中 72.5%的患者既往接受过至少两种化疗药物治疗，并接受了中位数为 6 周期 trabectedin/PLD 治疗（范围：1-24 周期）。中位 PFS 为 9.46 个月（95%置信区间[CI]，7.9-10.9），中位总生存期（OS）为 23.56 个月（95%CI，18.1-34.1）。未接受抗血管生成药物治疗的患者获得了更大的中位 PFS（p<0.007）和 OS（p<0.048），这主要归因于两个人群之间的差异。24 名患者（11.0%）获得完全缓解，57 名患者（26.1%）获得部分缓解，客观缓解率（ORR）为 37.2%。59 名患者（27.1%）疾病稳定，疾病控制率为 64.2%。BRCA1/2 状态和铂类敏感性对 PFS、OS 或 ORR 无统计学显著影响。最常见的 3/4 级不良事件（AE）为中性粒细胞减少症（30.3%）、贫血（6.4%）、血小板减少症（5.5%）和乏力（5.0%）。未发生与治疗相关的 AE 或意外 AE 导致的死亡。
trabectedin/PLD 联合治疗对 PS-ROC 患者具有临床意义且安全，无论患者是否接受过抗血管生成药物治疗，这与临床试验中选择的和预处理较少的患者观察到的结果一致。
这项在欧洲 57 个参考中心进行的非干预性、前瞻性研究一致证实，trabectedin 联合多柔比星脂质体在常规临床实践中是铂类敏感复发性卵巢癌女性患者的一种有临床意义且安全的选择。尽管研究人群代表的是比前瞻性临床试验中更具异质性、年龄更大、预处理更多的患者，但 trabectedin 联合 PLD 诱导了相当的临床获益，具有相似且可管理的安全性特征。总体而言，这些发现表明 trabectedin 联合 PLD 在真实临床实践中用于治疗大量预处理的患者时，仍具有抗肿瘤活性。
