Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
Rucaparib in Men With Metastatic Castration-Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration.
复制标题
具有转移性cast割前列腺癌的男性的鲁卡巴里（Rucaparib）具有BRCA1或BRCA2基因改变。
DOI：
10.1200/jco.20.01035
复制
发表时间：
2020-11-10
期刊：
影响因子：
--
通讯作者：
TRITON2 investigators
中科院分区：
文献类型：
--
作者：
Abida W;Patnaik A;Campbell D;Shapiro J;Bryce AH;McDermott R;Sautois B;Vogelzang NJ;Bambury RM;Voog E;Zhang J;Piulats JM;Ryan CJ;Merseburger AS;Daugaard G;Heidenreich A;Fizazi K;Higano CS;Krieger LE;Sternberg CN;Watkins SP;Despain D;Simmons AD;Loehr A;Dowson M;Golsorkhi T;Chowdhury S;TRITON2 investigators
BRCA1或BRCA2 （BRCA）改变在转移性去势抵抗性前列腺癌（mCRPC）患者中很常见，并可能导致对聚adp核糖聚合酶抑制剂的敏感性。我们介绍了在TRITON2 II期研究中，用鲁卡帕尼600毫克每日两次治疗伴有BRCA改变的mCRPC患者的结果。我们招募了在接受一到两条新一代雄激素受体定向治疗和一种紫杉烷为基础的mCRPC化疗后进展的患者。疗效和安全性人群包括接受≥1剂量rucaparib的有害BRCA改变的患者。关键疗效终点是客观缓解率（ORR；根据RECIST/前列腺癌临床试验工作组3，通过盲法、独立放射学审查和研究者评估的可测量疾病患者的客观缓解率）和局部评估的前列腺特异性抗原（PSA）反应（比基线降低≥50%）率。疗效和安全性人群包括115例BRCA改变的患者，伴有或不伴有可测量的疾病。经独立放射学检查和研究者评估确认的orr分别为43.5% （95% CI， 31.0%至56.7%；62例患者中有27例）和50.8% （95% CI， 38.1%至63.4%；65例患者中有33例）。确诊的PSA缓解率为54.8% （95% CI， 45.2%至64.1%；115例患者中有63例）。生殖系或体细胞BRCA改变患者与BRCA1或BRCA2改变患者的orr相似，而BRCA2改变患者的PSA反应率更高。最常见的≥3级治疗不良事件是贫血（25.2%，115例患者中有29例）。Rucaparib在mCRPC和有害BRCA改变患者中具有抗肿瘤活性，但具有与其他实体肿瘤类型一致的可管理的安全性。
BRCA1 or BRCA2 (BRCA) alterations are common in men with metastatic castration-resistant prostate cancer (mCRPC) and may confer sensitivity to poly(ADP-ribose) polymerase inhibitors. We present results from patients with mCRPC associated with a BRCA alteration treated with rucaparib 600 mg twice daily in the phase II TRITON2 study. We enrolled patients who progressed after one to two lines of next-generation androgen receptor–directed therapy and one taxane-based chemotherapy for mCRPC. Efficacy and safety populations included patients with a deleterious BRCA alteration who received ≥ 1 dose of rucaparib. Key efficacy end points were objective response rate (ORR; per RECIST/Prostate Cancer Clinical Trials Working Group 3 in patients with measurable disease as assessed by blinded, independent radiology review and by investigators) and locally assessed prostate-specific antigen (PSA) response (≥ 50% decrease from baseline) rate. Efficacy and safety populations included 115 patients with a BRCA alteration with or without measurable disease. Confirmed ORRs per independent radiology review and investigator assessment were 43.5% (95% CI, 31.0% to 56.7%; 27 of 62 patients) and 50.8% (95% CI, 38.1% to 63.4%; 33 of 65 patients), respectively. The confirmed PSA response rate was 54.8% (95% CI, 45.2% to 64.1%; 63 of 115 patients). ORRs were similar for patients with a germline or somatic BRCA alteration and for patients with a BRCA1 or BRCA2 alteration, while a higher PSA response rate was observed in patients with a BRCA2 alteration. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (25.2%; 29 of 115 patients). Rucaparib has antitumor activity in patients with mCRPC and a deleterious BRCA alteration, but with a manageable safety profile consistent with that reported in other solid tumor types.