Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, United States of America.
NRG Oncology SDMC, CTD Division, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
Gynecol Oncol. 2021 May;161(2):512-515. doi: 10.1016/j.ygyno.2021.01.037. Epub 2021 Feb 17.
To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651).
This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates.
Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes.
Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.
评估在一项 GOG Ⅰ期研究（GOG 9923，NCT00989651）中，按 BRCA 状态分层的上皮性卵巢癌（EOC）女性患者对接受维利帕利和贝伐珠单抗（bev）的静脉（IV）或腹腔（IP）化疗的耐受性。
这是一项经机构审查委员会批准的多中心前瞻性研究（GOG 9923）的未计划的事后分析。根据 BRCA 状态评估了临床特征和毒性数据，并使用描述性统计来总结基线患者特征和毒性。使用 Kaplan-Meier 法生成生存估计。
424 例患者可评估。患者接受 IV 卡铂、紫杉醇和 bev，每 21 天（方案 1），每周 IV 紫杉醇联合卡铂和 bev（方案 2）或 IV 紫杉醇联合 IP 顺铂（方案 3）。所有方案中 bev 均作为维持治疗。在这些方案中，维利帕利连续每天两次给药（连续）或在每个周期的 -2 至 5 天（间歇）。方案 1 中 10%的患者、方案 2 中 12%的患者和方案 3 中 19.8%的患者患有 BRCA 相关肿瘤。与野生型相比，BRCA 相关肿瘤患者发生贫血、发热性中性粒细胞减少症、腹痛、结肠穿孔、恶心、呕吐和周围感觉神经病的比率相似。BRCA 相关癌症和野生型癌症的中位无进展生存期（PFS）无显著差异（HR 0.96，CI 0.65-1.42），尽管本研究的主要目的不是评估结局。
胚系 BRCA 突变对 EOC 的化疗敏感性有积极影响，但 BRCA 相关肿瘤和 BRCA 野生型肿瘤之间的毒性差异以前尚未报道。在新诊断为卵巢癌的人群中，两组之间未观察到报告的毒性差异。
