美国德克萨斯大学安德森医学中心Robert L. Coleman研究小组分析了维利帕尼一线化疗与维持治疗对卵巢癌的疗效。该项研究成果在线发表在2019年9月28日出版的《新英格兰医学杂志》上。

目前，对于高级别浆液性卵巢癌患者，使用聚腺苷二磷酸核糖聚合酶抑制剂（如维利帕尼）联合化疗与维持治疗来进行初始治疗的临床数据很有限。

在这项国际性、临床3期、安慰剂对照试验中，研究组招募了1140名III至IV期高级别浆液性卵巢癌患者，按1：1：1随机分组，分别接受化疗+安慰剂，安慰剂维持治疗（对照组）；化疗+维利帕尼，安慰剂维持治疗（仅维利帕尼联合化疗组）；化疗+维利帕尼，维利帕尼维持治疗（维利帕尼全程组）。联合化疗6个周期，维持治疗30个周期。

在BRCA突变的患者中，维利帕尼全程组的中位无进展生存期为34.7个月，对照组为22.0个月，进展或死亡的风险比为0.44；在同源重组缺陷（HRD）的患者中分别为31.9个月和20.5个月，风险比为0.57；在整个意向治疗人群中则分别为23.5个月和17.3个月，风险比为0.68。维利帕尼联合化疗增加了贫血、血小板减少、恶心、疲劳等不良反应的发生率。

总之，对于晚期浆液性卵巢癌患者，卡铂+紫杉醇+维利帕尼诱导治疗以及维利帕尼维持治疗的方案，与单独卡铂+紫杉醇诱导治疗方案相比，显著延长了无进展生存期。

附：英文原文

Title: Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

Author: Robert L. Coleman, Gini F. Fleming, Mark F. Brady, Elizabeth M. Swisher, Karina D. Steffensen, Michael Friedlander, Aikou Okamoto, Kathleen N. Moore, Noa Efrat Ben-Baruch, Theresa L. Werner, Noelle G. Cloven, Ana Oaknin, Paul A. DiSilvestro, Mark A. Morgan, Joo-Hyun Nam, Charles A. Leath III, Shibani Nicum, Andrea R. Hagemann, Ramey D. Littell, David Cella, Sally Baron-Hay, Jesus Garcia-Donas, Mika Mizuno, Katherine Bell-McGuinn, Danielle M. Sullivan, Bruce A. Bach, Sudipta Bhattacharya, Christine K. Ratajczak, Peter J. Ansell, Minh H. Dinh, Carol Aghajanian, Michael A. Bookman

Issue&Volume: 2019-09-28

Abstract:

BACKGROUND
Data are limited regarding the use of poly(adenosine diphosphate [ADP]–ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma.

METHODS
In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population.

RESULTS
A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall.

CONCLUSIONS
Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear.

DOI: 10.1056/NEJMoa1909707

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1909707