Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2021 Jan;26(1):e164-e172. doi: 10.1002/onco.13551. Epub 2020 Oct 20.
On December 19, 2018, the U.S. Food and Drug Administration (FDA) granted approval to olaparib monotherapy for first-line maintenance treatment of BRCA-mutated (BRCAm) advanced ovarian cancer and, on May 8, 2020, expanded the indication of olaparib to include its use in combination with bevacizumab for first-line maintenance treatment of homologous recombination deficient (HRD)-positive advanced ovarian cancer. Both these approvals were based on randomized, double-blind, placebo-controlled trials. Approval for olaparib monotherapy was based on the SOLO-1 trial, comparing the efficacy of olaparib versus placebo in patients with BRCAm advanced ovarian, fallopian tube, or primary peritoneal cancer after surgical cytoreduction and first-line platinum-based chemotherapy. Two companion diagnostic (CDx) tests were approved with this indication: BRACAnalysis CDx, for germline BRCA1/2 alterations, and FoundationOne CDx, for BRCA1/2 alterations in tissue specimens. Approval for olaparib in combination with bevacizumab was based on the results of the PAOLA-1 trial that compared olaparib with bevacizumab versus placebo plus bevacizumab in patients with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer after first-line platinum-based chemotherapy and bevacizumab. Myriad myChoice CDx was designated as a companion diagnostic device for use of olaparib plus bevacizumab combination for ovarian cancer associated with HRD-positive status. Both trials demonstrated clinically meaningful improvements in progression-free survival and favorable benefit-risk profiles for the indicated populations. This article summarizes the FDA thought process and data supporting the approval of olaparib as monotherapy and in combination with bevacizumab for maintenance therapy in this setting. IMPLICATIONS FOR PRACTICE: These approvals represent the first poly (ADP-ribose) polymerase inhibitor, alone or in combination with bevacizumab, approved in first-line maintenance treatment of women with advanced ovarian cancer after cytoreductive surgery and chemotherapy. In patients with BRCA-mutated tumors, olaparib monotherapy demonstrated a 70% reduction in the risk of disease progression or death compared with placebo, and olaparib in combination with bevacizumab demonstrated a 67% reduction in the risk of disease progression or death compared with bevacizumab alone in homologous recombination deficient-positive tumors. These approvals represent a major advance for the treatment of women with advanced ovarian cancer who are in complete or partial response after their initial platinum-based chemotherapy.
2018 年 12 月 19 日，美国食品和药物管理局（FDA）批准奥拉帕利单药用于 BRCA 突变（BRCAm）晚期卵巢癌的一线维持治疗，2020 年 5 月 8 日，奥拉帕利的适应证扩展至包含其与贝伐珠单抗联合用于同源重组缺陷（HRD）阳性晚期卵巢癌的一线维持治疗。这两项批准均基于随机、双盲、安慰剂对照试验。奥拉帕利单药的批准基于 SOLO-1 试验，该试验比较了奥拉帕利与安慰剂在接受手术减瘤和一线铂类化疗后的 BRCAm 晚期卵巢、输卵管或原发性腹膜癌患者中的疗效。该适应证批准了两项伴随诊断（CDx）检测：BRACAnalysis CDx，用于种系 BRCA1/2 改变，FoundationOne CDx，用于组织标本中 BRCA1/2 改变。奥拉帕利联合贝伐珠单抗的批准基于 PAOLA-1 试验结果，该试验比较了奥拉帕利联合贝伐珠单抗与安慰剂联合贝伐珠单抗在一线铂类化疗和贝伐珠单抗治疗后晚期高级别上皮性卵巢癌、输卵管或原发性腹膜癌患者中的疗效。Myriad myChoice CDx 被指定为用于与 HRD 阳性状态相关的卵巢癌的奥拉帕利联合贝伐珠单抗联合治疗的伴随诊断设备。这两项试验均显示出对无进展生存期的临床意义的改善，并且对所指示的人群具有有利的风险获益特征。本文总结了 FDA 的思维过程和支持奥拉帕利作为单药以及在这种情况下与贝伐珠单抗联合用于维持治疗的批准的数据。
这些批准代表了首个聚（ADP-核糖）聚合酶抑制剂，单独或与贝伐珠单抗联合，在细胞减灭术和化疗后用于晚期卵巢癌的一线维持治疗。在 BRCA 突变肿瘤患者中，与安慰剂相比，奥拉帕利单药治疗使疾病进展或死亡的风险降低了 70%，而在同源重组缺陷阳性肿瘤患者中，奥拉帕利联合贝伐珠单抗治疗使疾病进展或死亡的风险降低了 67%。这些批准代表了在初始铂类化疗后完全或部分缓解的晚期卵巢癌女性治疗的重大进展。
