FDA Approval Summary: Polatuzumab Vedotin in the First-Line Treatment of Select Large B-cell Lymphomas.

IF 10 1区 医学 Q1 ONCOLOGY
Maryam Sarraf Yazdy,Yvette L Kasamon,Wenjuan Gu,Lisa R Rodriguez,Susan Jin,Vishal Bhatnagar,Nicholas C Richardson,Marc R Theoret,Richard Pazdur,Nicole J Gormley
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引用次数: 0

Abstract

In April 2023, the U.S. Food and Drug Administration granted regular approval to polatuzumab vedotin-piiq in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (pola+R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma, not otherwise specified or high-grade B-cell lymphoma and who have an International Prognostic Index score of 2 or greater. Approval was based on POLARIX, a randomized, double-blinded, placebo-controlled trial evaluating the superiority of substituting vincristine with polatuzumab vedotin in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen as first-line therapy for patients with large B-cell lymphoma (LBCL). Efficacy was based on investigator-assessed progression-free survival (PFS) in 879 patients who were randomized to receive pola+R-CHP or R-CHOP, followed by two cycles of rituximab alone. PFS was statistically significantly longer with pola+R-CHP with a HR of 0.73 [95% CI: 0.57, 0.95] and log-rank p-value of 0.0177 (two-sided α=0.05). There was no improvement demonstrated in the key secondary endpoints of CR rate at the end of therapy or overall survival (OS). Several issues raised uncertainty about the benefit-risk of polatuzumab vedotin in this curative-intent setting including the modest PFS benefit of pola+R-CHP and lack of OS benefit. The application was therefore presented at an Oncology Drug Advisory Committee. This article summarizes key aspects of the regulatory review, including perspectives on PFS and OS results and other endpoints.
FDA 批准摘要:Polatuzumab Vedotin 用于部分大 B 细胞淋巴瘤的一线治疗。
2023年4月,美国食品和药物管理局常规批准了polatuzumab vedotin-piiq与利妥昔单抗产品、环磷酰胺、多柔比星和泼尼松(pola+R-CHP)联合用于既往未经治疗的弥漫大B细胞淋巴瘤(未另作规定)或高级别B细胞淋巴瘤且国际预后指数为2分或以上的成人患者。POLARIX是一项随机、双盲、安慰剂对照试验,评估了在利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松(R-CHOP)方案中用泊拉珠单抗维多汀替代长春新碱作为大B细胞淋巴瘤(LBCL)患者一线疗法的优越性。879名患者随机接受了波拉+R-CHP或R-CHOP治疗,随后接受了两个周期的利妥昔单抗治疗,疗效以研究者评估的无进展生存期(PFS)为依据。从统计学角度看,接受 pola+R-CHP 治疗的 PFS 明显更长,HR 为 0.73 [95% CI:0.57, 0.95],对数秩 P 值为 0.0177(双侧 α=0.05)。在治疗结束时的CR率或总生存期(OS)这两个关键次要终点上,研究结果均无改善。有几个问题引起了人们对在这种以治愈为目的的治疗中使用泊拉珠单抗维多汀的效益-风险的不确定性,其中包括泊拉+R-CHP的PFS效益不高以及缺乏OS效益。因此,该申请被提交给了肿瘤药物咨询委员会。本文总结了监管审查的主要方面,包括对PFS和OS结果及其他终点的看法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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