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奥拉帕利辅助治疗BRCA1或BRCA2突变乳腺癌患者可显著延长生存期
作者:小柯机器人 发布时间:2021/6/6 21:36:18

英国伦敦癌症研究所Andrew N.J. Tutt团队研究了奥拉帕利辅助治疗BRCA1或BRCA2突变乳腺癌患者对预后的影响。2021年6月3日,《新英格兰医学杂志》发表了该成果。

聚(腺苷二磷酸核糖)聚合酶抑制剂靶向具有合成致死性的同源重组修复缺陷的癌症。需要新的治疗方法来减少BRCA1或BRCA2种系突变相关早期乳腺癌患者的复发。

研究组进行了一项临床3期、双盲、随机试验,招募接受局部治疗和新辅助或辅助化疗的人表皮生长因子受体2(HER2)阴性、BRCA1或BRCA2种系致病性或可能致病性突变以及高危临床病理因素的早期乳腺癌患者。将其按1:1随机分配,分别口服奥拉帕利或安慰剂1年。主要终点是侵袭性无病生存。

共有1836名患者接受了随机分组。在预先指定的事件驱动中期分析中,平均随访2.5年后,奥拉帕利组和安慰剂组的3年侵袭性无病生存率分别为85.9%和77.1%,组间差异显著。奥拉帕利组的3年无病生存率为87.5%,显著高于安慰剂组的80.4%。

与安慰剂相比,奥拉帕利的死亡率较低(分别死亡59和86例);然而,在P值小于0.01的中期分析边界,组间差异不显著。安全性数据与奥拉帕利已知副作用一致,没有过度的严重不良事件或特别关注的不良事件。

研究结果表明,在高危、HER2阴性的早期乳腺癌和种系BRCA1或BRCA2致病性或可能的致病性突变患者中,完成局部治疗和新辅助或辅助化疗后口服奥拉帕利,无侵袭性或远端疾病的生存期均显著长于安慰剂组。

附:英文原文

Title: Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer | NEJM

Author: Andrew N.J. Tutt, M.B., Ch.B., Ph.D.,, Judy E. Garber, M.D., M.P.H.,, Bella Kaufman, M.D.,, Giuseppe Viale, M.D.,, Debora Fumagalli, M.D., Ph.D.,, Priya Rastogi, M.D.,, Richard D. Gelber, Ph.D.,, Evandro de Azambuja, M.D., Ph.D.,, Anitra Fielding, M.B., Ch.B.,, Judith Balmaa, M.D., Ph.D.,, Susan M. Domchek, M.D.,, Karen A. Gelmon, M.D.,, Simon J. Hollingsworth, Ph.D.,, Larissa A. Korde, M.D., M.P.H.,, Barbro Linderholm, M.D., Ph.D.,, Hanna Bandos, Ph.D.,, Elbieta Senkus, M.D., Ph.D.,, Jennifer M. Suga, M.D.,, Zhimin Shao, M.D.,, Andrew W. Pippas, M.D.,, Zbigniew Nowecki, M.D., Ph.D.,, Tomasz Huzarski, M.D., Ph.D.,, Patricia A. Ganz, M.D.,, Peter C. Lucas, M.D., Ph.D.,, Nigel Baker, M.Sc.,, Sibylle Loibl, M.D., Ph.D.,, Robin McConnell, M.Sc.,, Martine Piccart, M.D., Ph.D.,, Rita Schmutzler, M.D., Dr.Med.Habil.,, Guenther G. Steger, M.D.,, Joseph P. Costantino, Dr.P.H.,, Amal Arahmani, Ph.D.,, Norman Wolmark, M.D.,, Eleanor McFadden, M.A.,, Vassiliki Karantza, M.D., Ph.D.,, Sunil R. Lakhani, M.D.,, Greg Yothers, Ph.D.,, Christine Campbell, M.Sc.,, and Charles E. Geyer, Jr., M.D.

Issue&Volume: 2021-06-03

Abstract:

Background

Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation–associated early breast cancer.

Methods

We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease–free survival.

Results

A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease–free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest.

Conclusions

Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.

DOI: 10.1056/NEJMoa2105215

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2105215

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home