法国莱昂贝拉德中心Isabelle Ray-Coquard研究团队宣布他们探讨了奥拉帕利+贝伐珠单抗一线维持治疗卵巢癌的效果。这一研究成果于2019年12月19日发表在国际顶尖学术期刊《新英格兰医学杂志》上。

对于新诊断的BRCA突变的晚期卵巢癌患者，奥拉帕利维持治疗效果显著。但对于伴或不伴BRCA突变的卵巢癌患者，奥拉帕利联合贝伐珠单抗维持治疗的效果尚未清楚。

研究组进行了一项随机、双盲、国际、临床3期试验，招募了806名新诊断、晚期、高级别的卵巢癌患者，均伴或不伴BRCA突变，在铂-紫杉醇-贝伐珠单抗一线治疗后有所缓解。按2：1将患者随机分组，537名接受奥拉帕利治疗，269名接受安慰剂治疗，为期24个月，同时两组患者均接受贝伐珠单抗治疗，每3周一次，持续15个月。

中位随访22.9个月后，奥拉帕利组的中位无进展生存期为22.1个月，安慰剂组为16.6个月，差异显著。BRCA突变的同源重组缺陷（HRD）阳性的肿瘤患者疾病进展和死亡的风险比为0.33，奥拉帕利组和安慰剂组的中位无进展生存期分别为37.2个月和17.7个月；没有BRCA突变的HRD阳性肿瘤患者的风险比为0.43，奥拉帕利组和安慰剂组的中位无进展生存期分别为28.1个月和16.6个月。不良事件符合奥拉帕利和贝伐珠单抗的安全性。

总之，在接受包括贝伐珠单抗在内的一线标准治疗的晚期卵巢癌患者中，添加奥拉帕利维持治疗可显著延长无进展生存期，其中HRD阳性的肿瘤患者获益最大。

附：英文原文

Title: Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

Author: Isabelle Ray-Coquard, M.D., Ph.D.,, Patricia Pautier, M.D.,, Sandro Pignata, M.D., Ph.D.,, David Pérol, M.D.,, Antonio González-Martín, M.D., Ph.D.,, Regina Berger, Ph.D.,, Keiichi Fujiwara, M.D., Ph.D.,, Ignace Vergote, M.D., Ph.D.,, Nicoletta Colombo, M.D.,, Johanna Menp, M.D., Ph.D.,, Frédéric Selle, M.D.,, Jalid Sehouli, M.D.,, Domenica Lorusso, M.D.,, Eva M. Guerra Alía, M.D.,, Alexander Reinthaller, M.D.,, Shoji Nagao, M.D., Ph.D.,, Claudia Lefeuvre-Plesse, M.D.,, Ulrich Canzler, M.D.,, Giovanni Scambia, M.D.,, Alain Lortholary, M.D.,, Frederik Marmé, M.D.,, Pierre Combe, M.D.,, Nikolaus de Gregorio, M.D., Ph.D.,, Manuel Rodrigues, M.D., Ph.D.,, Paul Buderath, M.D.,, Coraline Dubot, M.D.,, Alexander Burges, M.D.,, Benot You, M.D.,, Eric Pujade-Lauraine, M.D., Ph.D.,, and Philipp Harter, M.D., Ph.D.

Issue&Volume: 2019-12-18

Abstract: 

BACKGROUND
Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown.

METHODS
We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum–taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or BRCA mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death.

RESULTS
Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had BRCA mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have BRCA mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab.

CONCLUSIONS
In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenance olaparib provided a significant progression-free survival benefit, which was substantial in patients with HRD-positive tumors, including those without a BRCA mutation.

DOI: 10.1056/NEJMoa1911361

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1911361