法国巴黎萨克雷大学Karim Fizazi团队研究了Rucaparib治疗转移性前列腺癌对患者预后的影响。这一研究成果发表在2023年2月16日出版的《新英格兰医学杂志》上。

在一项2期临床研究中，多聚ADP-核糖聚合酶（PARP）抑制剂Rucaparib在患有转移性、去势耐受性前列腺癌症并伴有有害BRCA改变的患者中表现出高水平的活性。仍需数据来确认和扩展2期研究的结果。

在这项随机、对照、3期临床试验中，研究组招募了患有转移性、去势耐受性前列腺癌症并伴有BRCA1、BRCA2或ATM改变的患者，这些患者在使用第二代雄激素受体途径抑制剂（ARPI）治疗后疾病进展。研究组以2:1的比例随机分配患者接受口服rucaparib（600mg，每天两次）或医生选择的对照药物（多西他赛或第二代ARPI[乙酸阿比特罗或恩扎鲁胺]）。根据独立审查，主要结局是影像学无进展生存期的中位数。

在接受过预筛选或筛查的4855名患者中，270名被分配接受rucaparib，135人接受对照药物（意向治疗人群）；在两组中，分别有201名患者和101名患者BRCA改变。在62个月时，基于影像学的无进展生存期，BRCA亚组中位数分别为11.2个月和6.4个月，危险比为0.50；意向治疗组中位数为10.2个月和6.4个月，风险比为0.61。在ATM亚组的一项探索性分析中，基于影像学的无进展生存期中位值在rucaparib组为8.1个月，在对照组为6.8个月（危险比为0.95）。Rucaparib最常见的不良事件是疲劳和恶心。

研究结果表明，在BRCA改变的转移性去势抵抗性前列腺癌患者中，rucaparib的基于影像学的无进展生存期明显长于对照药物。

附：英文原文

Title: Rucaparib or Physician’s Choice in Metastatic Prostate Cancer | NEJM

Author: Karim Fizazi, M.D., Ph.D.,, Josep M. Piulats, M.D., Ph.D.,, M. Neil Reaume, M.D.,, Peter Ostler, M.D.,, Ray McDermott, M.B., B.Ch., B.A.O., Ph.D.,, Joel R. Gingerich, M.D.,, Elias Pintus, M.D.,, Srikala S. Sridhar, M.D.,, Richard M. Bambury, M.D.,, Urban Emmenegger, M.D.,, Henriette Lindberg, M.D., Ph.D.,, David Morris, M.D.,, Franco Nolè, M.D.,, John Staffurth, M.D.,, Charles Redfern, M.D.,, María I. Sáez, M.D.,, Wassim Abida, M.D., Ph.D.,, Gedske Daugaard, M.D., D.M.Sc.,, Axel Heidenreich, M.D.,, Laurence Krieger, M.D.,, Brieuc Sautois, M.D., Ph.D.,, Andrea Loehr, Ph.D.,, Darrin Despain, M.S.,, Catherine A. Heyes, B.Sc.,, Simon P. Watkins, Ph.D.,, Simon Chowdhury, M.D., Ph.D.,, Charles J. Ryan, M.D.,, and Alan H. Bryce, M.D.

Issue&Volume: 2023-02-16

Abstract:

Background

In a phase 2 study, rucaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), showed a high level of activity in patients who had metastatic, castration-resistant prostate cancer associated with a deleterious BRCA alteration. Data are needed to confirm and expand on the findings of the phase 2 study.

Methods

In this randomized, controlled, phase 3 trial, we enrolled patients who had metastatic, castration-resistant prostate cancer with a BRCA1, BRCA2, or ATM alteration and who had disease progression after treatment with a second-generation androgen-receptor pathway inhibitor (ARPI). We randomly assigned the patients in a 2:1 ratio to receive oral rucaparib (600 mg twice daily) or a physician’s choice control (docetaxel or a second-generation ARPI [abiraterone acetate or enzalutamide]). The primary outcome was the median duration of imaging-based progression-free survival according to independent review.

Results

Of the 4855 patients who had undergone prescreening or screening, 270 were assigned to receive rucaparib and 135 to receive a control medication (intention-to-treat population); in the two groups, 201 patients and 101 patients, respectively, had a BRCA alteration. At 62 months, the duration of imaging-based progression-free survival was significantly longer in the rucaparib group than in the control group, both in the BRCA subgroup (median, 11.2 months and 6.4 months, respectively; hazard ratio, 0.50; 95% confidence interval [CI], 0.36 to 0.69) and in the intention-to-treat group (median, 10.2 months and 6.4 months, respectively; hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001 for both comparisons). In an exploratory analysis in the ATM subgroup, the median duration of imaging-based progression-free survival was 8.1 months in the rucaparib group and 6.8 months in the control group (hazard ratio, 0.95; 95% CI, 0.59 to 1.52). The most frequent adverse events with rucaparib were fatigue and nausea.

Conclusions

The duration of imaging-based progression-free survival was significantly longer with rucaparib than with a control medication among patients who had metastatic, castration-resistant prostate cancer with a BRCA alteration.

DOI: 10.1056/NEJMoa2214676

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2214676