他唑帕利联合恩杂鲁胺治疗转移性耐受性前列腺癌：随机、安慰剂对照、III 期 TALAPRO-2 研究的安全性分析

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-10-20 DOI:10.1016/j.ejca.2024.115078

Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal

{"title":"他唑帕利联合恩杂鲁胺治疗转移性耐受性前列腺癌：随机、安慰剂对照、III 期 TALAPRO-2 研究的安全性分析","authors":"Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal","doi":"10.1016/j.ejca.2024.115078","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>","PeriodicalId":11980,"journal":{"name":"European Journal of Cancer","volume":null,"pages":null},"PeriodicalIF":7.6000,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study\",\"authors\":\"Arun A. Azad , Karim Fizazi , Nobuaki Matsubara , Fred Saad , Ugo De Giorgi , Jae Young Joung , Peter C.C. Fong , Robert J. Jones , Stefanie Zschäbitz , Jan Oldenburg , Neal D. Shore , Curtis Dunshee , Joan Carles , Andre P. Fay , Xun Lin , Liza DeAnnuntis , Nicola Di Santo , Michael A. Zielinski , Neeraj Agarwal\",\"doi\":\"10.1016/j.ejca.2024.115078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.</div></div><div><h3>Methods</h3><div>The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.</div></div><div><h3>Results</h3><div>In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).</div></div><div><h3>Conclusion</h3><div>Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.</div></div><div><h3>ClinicalTrials.gov Identifier</h3><div>NCT03395197</div></div>\",\"PeriodicalId\":11980,\"journal\":{\"name\":\"European Journal of Cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2024-10-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0959804924012097\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Cancer","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959804924012097","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景这项详细分析进一步描述了正在进行的针对转移性耐受性前列腺癌（mCRPC）患者的随机III期TALAPRO-2研究中，talazoparib联合恩杂鲁胺的安全性特征。在全基因组和同源重组修复（HRR）缺陷人群中，与安慰剂加恩杂鲁胺相比，talazoparib加恩杂鲁胺可显著改善无放射进展生存期。方法TALAPRO-2中的他拉唑帕利+恩杂鲁胺安全人群包括队列1中的398名患者（所有来访者，未选择HRR基因改变者）和合并HRR缺陷人群中的198名患者（所有来访者中HRR基因改变者加上随后入组的HRR基因改变者；队列2）。患者接受塔拉帕利 0.5 毫克（0.35 毫克，中度肾功能损害）和恩扎鲁胺 160 毫克的治疗，每天一次。安全性分析评估了常见的治疗突发不良事件（TEAE）、其类型、严重程度、时间、严重性以及与研究治疗的关系。结果在所有患者（n = 398）和HRR缺陷人群（n = 198）中，分别有71.9%和66.2%的患者报告了使用talazoparib加恩杂鲁胺的全因3/4级（G3/4）TEAE。最常见的G3/4血液学TEAE为贫血（分别为46.7%和40.9%）、中性粒细胞减少（分别为18.3%和18.7%）和血小板减少（分别为7.3%和7.1%）。G3/4贫血症的中位发生时间分别为3.3个月和3.3个月，G3/4中性粒细胞减少症的中位发生时间分别为2.3个月和2.3个月，G3/4血小板减少症的中位发生时间分别为2.3个月和1.5个月。血红蛋白的最大降幅出现在治疗 13 周和 15 周之后。分别有18.8%和10.1%的患者停用了talazoparib。通过中断剂量（62.1%和57.6%）、减少剂量（52.8%和52.0%）、血液学支持治疗（13.1%和10.6%）和输注红细胞（39.2%和35.9%）等方法处理了TEAEs。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study

Background

This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.

Methods

The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2). Patients received talazoparib 0.5 mg (0.35 mg, moderate renal impairment) and enzalutamide 160 mg once daily. Safety analyses evaluated common treatment-emergent adverse events (TEAE), their type, severity, timing, seriousness, and relationship to study treatment.

Results

In the all-comers (n = 398) and HRR-deficient populations (n = 198), all-cause grade 3/4 (G3/4) TEAEs with talazoparib plus enzalutamide were reported in 71.9 % and 66.2 % of patients, respectively. Most common G3/4 hematologic TEAEs were anemia (46.7 % and 40.9 %, respectively), neutropenia (18.3 % and 18.7 %), and thrombocytopenia (7.3 % and 7.1 %). Median time to event was 3.3 and 3.3 months for G3/4 anemia, 2.3 and 2.3 months for G3/4 neutropenia, and 2.3 and 1.5 months for G3/4 thrombocytopenia. Maximum hemoglobin reduction occurred after 13 and 15 weeks of treatment. 18.8 % and 10.1 % of patients discontinued talazoparib. TEAEs were managed with dose interruption (62.1 % and 57.6 %), reduction (52.8 % and 52.0 %), hematologic supportive care (13.1 % and 10.6 %), and packed red blood cell transfusions (39.2 % and 35.9 %).

Conclusion

Talazoparib plus enzalutamide had a generally manageable safety profile in patients with mCRPC within the all-comers and the HRR-deficient populations.

ClinicalTrials.gov Identifier

NCT03395197

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.