Colombo Nicoletta
Institute of Oncology and University of Milan-Bicocca, Milan, Italy.
EJC Suppl. 2014 Dec;12(2):7-12. doi: 10.1016/S1359-6349(15)70004-2. Epub 2015 Jan 13.
The choice of second-line chemotherapy in patients with recurrent ovarian cancer (ROC) is complex, with several factors to be considered, the most important of which is the length of the platinum-free treatment interval (PFI). Recently ROC patients have been further stratified into platinum sensitive (PS), partially platinum sensitive (PPS) and platinum resistant (PR) subgroups depending on the length of the PFI. Response to second-line therapy, progression-free survival (PFS) and overall survival (OS) are linked to the PFI, all of them improving as the PFI increases. Consequently, there is increasing interest in PFI extension strategies with platinum-free therapeutic options. Such strategies are currently being studied in patients with partially platinum-sensitive disease (PFI 6-12 months), as the treatment of these patients remains clinically challenging. A non-platinum option, trabectedin + pegylated liposomal doxorubicin (PLD) combination, has been evaluated in ROC patients in the pivotal phase III OVA-301 study. The OVA-301 study differed from previous trials in the same setting as it included only patients who were not expected to benefit from or who were ineligible for or who were unwilling to receive re-treatment with platinum-based chemotherapy, including those with PPS and PR disease. Subset analysis of patients with PPS disease in OVA-301 showed that the trabectedin + PLD combination significantly improved PFS compared with PLD alone; median PFS 7.4 versus 5.5 months, p=0.0152. Final survival data from the same subset of patients, showed that trabectedin + PLD also achieved a significant 36% decrease in the risk of death compared with PLD alone (HR=0.64; 95% CI, 0.47-0.88; p=0.0027). Median overall survival (OS) was 22.4 months in the trabectedin + PLD arm versus 16.4 months in the PLD arm. This represents a statistically significant 6-month improvement in median OS in patients treated with trabectedin + PLD compared to those treated with PLD alone.
复发性卵巢癌(ROC)患者二线化疗方案的选择较为复杂,需考虑多个因素,其中最重要的是无铂治疗间隔(PFI)的时长。近来,根据PFI时长,ROC患者被进一步分为铂敏感(PS)、部分铂敏感(PPS)和铂耐药(PR)亚组。二线治疗的反应、无进展生存期(PFS)和总生存期(OS)均与PFI相关,随着PFI延长,这些指标均有所改善。因此,人们对采用无铂治疗方案延长PFI的策略越来越感兴趣。目前正在对部分铂敏感疾病(PFI为6 - 12个月)的患者进行此类策略的研究,因为这些患者的治疗在临床上仍然具有挑战性。在关键的III期OVA - 301研究中,已对一种非铂方案——曲贝替定 + 聚乙二醇化脂质体阿霉素(PLD)联合方案在ROC患者中进行了评估。OVA - 301研究与之前相同背景下的试验不同,因为它仅纳入了预计无法从铂类化疗再治疗中获益、不符合条件或不愿接受铂类化疗再治疗的患者,包括患有PPS和PR疾病的患者。OVA - 301中PPS疾病患者的亚组分析表明,与单纯使用PLD相比,曲贝替定 + PLD联合方案显著改善了PFS;中位PFS分别为7.4个月和5.5个月,p = 0.0152。同一亚组患者的最终生存数据显示,与单纯使用PLD相比,曲贝替定 + PLD联合方案还使死亡风险显著降低了36%(HR = 0.64;95% CI,0.47 - 0.88;p = 0.0027)。曲贝替定 + PLD组的中位总生存期(OS)为22.4个月,而PLD组为16.4个月。与单纯接受PLD治疗的患者相比,接受曲贝替定 + PLD治疗的患者中位OS在统计学上显著延长了6个月。
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