奧拉帕利+貝伐珠單抗一線維持治療卵巢癌效果顯著
作者：
小柯機器人發布時間：2019/12/20 14:23:53
法國萊昂貝拉德中心Isabelle Ray-Coquard研究團隊宣布他們探討了奧拉帕利+貝伐珠單抗一線維持治療卵巢癌的效果。這一研究成果於2019年12月19日發表在國際頂尖學術期刊《新英格蘭醫學雜誌》上。
對於新診斷的BRCA突變的晚期卵巢癌患者，奧拉帕利維持治療效果顯著。但對於伴或不伴BRCA突變的卵巢癌患者，奧拉帕利聯合貝伐珠單抗維持治療的效果尚未清楚。
研究組進行了一項隨機、雙盲、國際、臨床3期試驗，招募了806名新診斷、晚期、高級別的卵巢癌患者，均伴或不伴BRCA突變，在鉑-紫杉醇-貝伐珠單抗一線治療後有所緩解。按2：1將患者隨機分組，537名接受奧拉帕利治療，269名接受安慰劑治療，為期24個月，同時兩組患者均接受貝伐珠單抗治療，每3周一次，持續15個月。
中位隨訪22.9個月後，奧拉帕利組的中位無進展生存期為22.1個月，安慰劑組為16.6個月，差異顯著。BRCA突變的同源重組缺陷（HRD）陽性的腫瘤患者疾病進展和死亡的風險比為0.33，奧拉帕利組和安慰劑組的中位無進展生存期分別為37.2個月和17.7個月；沒有BRCA突變的HRD陽性腫瘤患者的風險比為0.43，奧拉帕利組和安慰劑組的中位無進展生存期分別為28.1個月和16.6個月。不良事件符合奧拉帕利和貝伐珠單抗的安全性。
總之，在接受包括貝伐珠單抗在內的一線標準治療的晚期卵巢癌患者中，添加奧拉帕利維持治療可顯著延長無進展生存期，其中HRD陽性的腫瘤患者獲益最大。
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