FDA Approval Summary: Olaparib Monotherapy or in Combination with Bevacizumab for the Maintenance Treatment of Patients with Advanced Ovarian Cancer.

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. Despite the best standard of care for newly diagnosed advanced ovarian cancer, approximately 70% of women relapse within the first 3 years. This article presents the FDA's rationale for approval of olaparib for the maintenance therapy of patients with deleterious or suspected deleterious germline or somatic BRCA‐mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first‐line platinum‐based chemotherapy. [ABSTRACT FROM AUTHOR]