From Gustave Roussy Institute, Paris-Saclay University, Villejuif, France (K.F.); Institut Català d'Oncologia-Bellvitge Institute for Biomedical Research -CiberOnc, Barcelona (J.M.P.), and the Medical Oncology Intercenter Unit, Regional and Virgen de la Victoria University Hospitals, IBIMA, Málaga (M.I.S.) - both in Spain; the Ottawa Hospital Research Institute, Ottawa (M.N.R.), CancerCare Manitoba, Winnipeg (J.R.G.), and Princess Margaret Cancer Centre (S.S.S.) and Odette Cancer Centre, Sunnybrook Health Sciences Centre (U.E.), Toronto - all in Canada; Mount Vernon Cancer Centre, Northwood (P.O.), Guy's Hospital (E.P.) and Guy's Hospital and Sarah Cannon Research Institute (S.C.), London, Velindre University NHS Trust, Cardiff (J.S.), and Clovis Oncology UK, Cambridge (C.A.H., S.P.W.) - all in the United Kingdom; St. Vincent's University Hospital and Cancer Trials Ireland, Dublin (R.M.), and Cork University Hospital, Wilton (R.M.B.) - both in Ireland; Herlev University Hospital, Herlev (H.L.), and Copenhagen University Hospital, Rigshospitalet, Copenhagen (G.D.) - both in Denmark; Urology Associates, Nashville (D.M.); European Institute of Oncology IRCCS, Milan (F.N.); Sharp HealthCare, San Diego, CA (C.R.); Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York (W.A.); Universitätsklinikum Köln, Cologne, Germany (A.H.); Medical University of Vienna, Vienna (A.H.); Genesis Care, North Shore, Sydney (L.K.); University Hospital of Liège, CHU Sart-Tilman, Liège, Belgium (B.S.); Clovis Oncology, Boulder, CO (A.L., D.D.); the University of Minnesota, Minneapolis (C.J.R.); and Mayo Clinic, Phoenix, AZ (A.H.B.).
N Engl J Med. 2023 Feb 23;388(8):719-732. doi: 10.1056/NEJMoa2214676. Epub 2023 Feb 16.
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 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 , , or 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 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 alteration. (Funded by Clovis Oncology; TRITON3 ClinicalTrials.gov number, NCT02975934.).
背景：在一项 2 期研究中，聚（ADP-核糖）聚合酶（PARP）抑制剂鲁卡帕尼在伴有有害改变的转移性去势抵抗性前列腺癌患者中表现出了较高的活性。需要数据来证实和扩展 2 期研究的结果。
方法：在这项随机、对照、3 期试验中，我们招募了转移性去势抵抗性前列腺癌患者，这些患者存在 、 或 改变，并且在接受第二代雄激素受体通路抑制剂（ARPI）治疗后疾病进展。我们以 2:1 的比例随机分配患者接受口服鲁卡帕尼（每天 2 次，每次 600 毫克）或医生选择的对照药物（多西他赛或第二代 ARPI[醋酸阿比特龙或恩扎鲁胺]）。主要终点是根据独立评估的影像学无进展生存期的中位数。
结果：在接受过预筛选或筛选的 4855 名患者中，270 名被分配接受鲁卡帕尼治疗，135 名接受对照药物治疗（意向治疗人群）；在这两组中，分别有 201 名和 101 名患者存在 改变。在 62 个月时，与对照组相比，鲁卡帕尼组的影像学无进展生存期明显更长，在 BRCA 亚组中（中位无进展生存期分别为 11.2 个月和 6.4 个月；风险比为 0.50；95%置信区间[CI]为 0.36 至 0.69）和意向治疗组（中位无进展生存期分别为 10.2 个月和 6.4 个月；风险比为 0.61；95%CI 为 0.47 至 0.80；两者均<0.001）。在 ATM 亚组的探索性分析中，鲁卡帕尼组的影像学无进展生存期中位数为 8.1 个月，对照组为 6.8 个月（风险比为 0.95；95%CI 为 0.59 至 1.52）。鲁卡帕尼最常见的不良反应是疲劳和恶心。
结论：在伴有 改变的转移性去势抵抗性前列腺癌患者中，与对照药物相比，鲁卡帕尼可显著延长影像学无进展生存期。（由 Clovis Oncology 资助；TRITON3 ClinicalTrials.gov 编号，NCT02975934。）
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