目的：本研究旨在评估GOG I期临床研究（GOG 9923，NCT00989651）中，不同BRCA状态患者对静脉或腹腔化疗联合维利帕尼和贝伐珠单抗治疗的耐受度。
Method: This is an Institutional Review Board approved, multiinstitutional, prospective study of women 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. Veliparib was given with cytotoxic chemotherapy either twice daily for the entirety of each cycle (continuous) or on days 2 to 5 (intermittent). Primary endpoints of maximum tolerated dose (MTD) and recommended phase 2 dose were presented at ASCO . This is an unplanned, post hoc analysis of clinical characteristics and toxicity data based on BRCA status. Descriptive statistics and Kaplan-Meier methods were used.
方法：本研究是一项机构审查委员会批准的多机构、前瞻性研究。研究对象接受卡铂+紫杉醇+贝伐珠单抗，静脉用药3周疗（方案1）；或卡铂+紫杉醇+贝伐珠单抗，静脉用药周疗（方案2）；或紫杉醇+贝伐珠单抗静脉用药，联合顺铂腹腔化疗（方案3）。所有治疗方案后贝伐珠单抗均作为维持治疗持续使用。在每个治疗周期内每天（连续方案）或在周期第2-5天（间歇方案）给予每日两次维利帕尼作为细胞毒性治疗。最大耐受剂量（MTD）和推荐的II期临床剂量作为主要终点，已在ASCO大会中报道。本文是计划外的，基于BRCA状态的，事后临床特征和毒性数据分析，采用了描述性统计和Kaplan-Meier方法。
Results: A total of 424 patients were evaluable. Of these, 173 (40.8%) were treated on regimen 1, 128 (30.2%) on regimen 2, and 123 (29%) on regimen 3. The majority of patients were 50–69 years old and Caucasian and had a performance status of 0–1. Serous histology (77.6%) was most common, followed by endometrioid (7.5%) and clear cell (5.9%). Eighty-five percent of patients in regimen I had grade 4–5 toxicities; 50% in regimen 2; and 45.5% in regimen 3. Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 were BRCApositive. BRCA-positive patients, when compared to wildtype patients, experienced similar rates of anemia (29.3% vs 27.2%, P = 0.73), febrile neutropenia (8.8% vs 9.1%, P = 0.92), abdominal pain (8.6% vs 4.8%, P = 0.26), colonic perforation (1.7% vs 1%, P = 0.62), nausea (6.9% vs 6.2%, P = 0.85), vomiting (5.2% vs 4.8%, P = 0.89), and peripheral sensory neuropathy (0% vs 1.4%, P = 0.36). Median progression-free survival was not significantly different between BRCA-positive and -negative patients (HR = 0.96, 95% CI 0.65–1.42), although this study’s primary aim was not to evaluate outcomes.
结果：共评估了424例患者，其中173例（40.8%）采用方案1治疗，128例（30.2%）采用方案2治疗，123例（29%）采用方案3治疗。多数患者是50-69岁的白种人，ECOG评分0-1分。最常见的是浆液性癌（77.6%），其次为子宫内膜样癌（7.5%）和透明细胞癌（5.9%）。方案1中85%的患者出现4-5级毒性反应；方案2中比例为50%；方案3中比例为45.5%。方案1、方案2和方案3治疗的患者中，分别有10%、12%和19.8%的BRCA突变阳性。与野生型患者相比，BRCA突变阳性患者的贫血（29.3% vs 27.2%，P=0.73）、
发热性中性粒细胞减少（8.8% vs 9.1%，P=0.92）、腹痛（8.6% vs 4.8%，P=0.26）、结肠穿孔（1.7% vs 1%，P=0.62）、恶心（6.9% vs 6.2%，P=0.85）、呕吐（5.2% vs 4.8%，P=0.89）以及外周感觉神经病变（0% vs 1.4%，P=0.36）的发生率相似。尽管本研究的主要目标不是评估治疗结局，BRCA突变阳性和阴性患者的中位无进展生存期无显著差异（HR=0.96，95% CI 0.65-1.42）。
Conclusion: Germline BRCA mutations positively affect chemosensitivity in epithelial ovarian cancer, but may also affect toxicities experienced by women with this disease. In this population with newly diagnosed ovarian cancer, however, we show that therapy is well tolerated among bothBRCA-positive and -negative patients.
结论：胚系BRCA基因突变对上皮性卵巢癌的化疗敏感性有显著影响，但也可能影响卵巢癌患者的药物毒性反应。然而，我们发现在新诊断卵巢癌人群中，不论BRCA基因突变与否，患者都能耐受治疗。
