Comparative efficacy and safety of talazoparib plus enzalutamide and other first-line treatments for metastatic castration-resistant prostate cancer.

IF 4.8 2区 医学 Q1 ONCOLOGY
Oncologist Pub Date : 2025-03-10 DOI:10.1093/oncolo/oyae237
Elena Castro, Jenna Ellis, Samantha Craigie, Anja Haltner, Jonathan Nazari, Alexander Niyazov, Imtiaz A Samjoo
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引用次数: 0

Abstract

Background: Talazoparib plus enzalutamide (TALA + ENZA) has demonstrated antitumor activity in the phase 3 clinical trial (TALAPRO-2; NCT03395197) as first-line (1L) therapy in men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC). Although many active interventions are available, randomized controlled trials (RCTs) involving talazoparib have only been conducted to assess its efficacy and safety compared to enzalutamide. To estimate comparisons between all relevant interventions, indirect comparisons are needed.

Objective: To estimate the comparative efficacy and safety of TALA + ENZA in 1L patients with mCRPC by conducting a systematic literature review and network meta-analyses (NMAs).

Methods: Databases were searched using Ovid, along with several gray literature sources to identify RCTs evaluating treatments in 1L mCRPC (PROSPERO registration: CRD42021283512). Feasibility assessment evaluated trial suitability for NMA inclusion and Bayesian or frequentist NMAs were conducted for evaluable efficacy and safety outcomes, respectively.

Results: Thirty-three RCTs met the eligibility criteria and were feasible for NMAs. Across multiple efficacy outcomes assessed, except for overall survival (OS), TALA + ENZA was ranked the most efficacious treatment. For OS, TALA + ENZA showed the second-highest probability of being the most effective treatment; second to docetaxel 50 mg plus prednisolone 10 mg. With respect to safety outcomes, TALA + ENZA, in general, showed increased rates of hematological adverse events.

Conclusions: TALA + ENZA showed favorable results across multiple efficacy endpoints, but not across hematological toxicities compared with other 1L treatments in asymptomatic or mildly symptomatic mCRPC in the all-comers patient population.

塔拉帕利联合恩杂鲁胺与其他一线治疗转移性耐受性前列腺癌药物的疗效和安全性比较。
背景:他唑帕利+恩杂鲁胺(TALA+ENZA)作为一线(1L)疗法治疗无症状或轻度症状的转移性去势抵抗性前列腺癌(mCRPC)男性患者的3期临床试验(TALAPRO-2;NCT03395197)已证明了其抗肿瘤活性。虽然目前有许多积极的干预措施,但涉及talazoparib的随机对照试验(RCT)仅用于评估其与恩扎鲁胺相比的疗效和安全性。为了估计所有相关干预措施之间的比较,需要进行间接比较:通过进行系统性文献综述和网络荟萃分析(NMAs),评估 TALA + ENZA 在 1L mCRPC 患者中的疗效和安全性比较:使用 Ovid 和一些灰色文献来源检索数据库,以确定评估 1L mCRPC 治疗方法的 RCT(PROSPERO 注册:CRD42021283512)。可行性评估对纳入 NMA 的试验适宜性进行了评估,并对可评估的疗效和安全性结果分别进行了贝叶斯或频数 NMA:结果:33 项 RCT 符合资格标准,可进行 NMA。在多项疗效评估结果中,除总生存期(OS)外,TALA + ENZA被评为疗效最好的治疗方法。在总生存期方面,TALA + ENZA成为最有效治疗方法的概率仅次于多西他赛50毫克加泼尼松龙10毫克。在安全性方面,TALA + ENZA的血液学不良事件发生率普遍上升:结论:TALA+ENZA在多个疗效终点方面都显示出良好的效果,但在血液学毒性方面,与其他1L疗法相比,TALA+ENZA对无症状或轻度症状的mCRPC患者群体的疗效并不理想。
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来源期刊
Oncologist
Oncologist 医学-肿瘤学
CiteScore
10.40
自引率
3.40%
发文量
309
审稿时长
3-8 weeks
期刊介绍: The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.
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