Olaparib plus Bevacizumab Has Been Approved as Maintenance Therapy for Ovarian, Fallopian Tube, or Primary Peritoneal Cancers

In late 2018, olaparib monotherapy was approved for first-line maintenance treatment of BRCA-mutated (BRCAm) advanced ovarian cancer. In May 2020, the indication was expanded to include its use in combination with bevacizumab for first-line maintenance treatment of homologous recombination deficient (HRD)-positive advanced ovarian cancer.¹

The expanded indication specifically focused on patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have shown complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with HRD-positive status characterized by either a BRCA mutation that is deleterious or suspected deleterious, in addition to or upon detected genomic instability.²

To ensure eligibility for treatment with frontline olaparib as maintenance therapy in combination with bevacizumab, the US Food and Drug Administration approved the Myriad myChoice CDx comprehensive tumor test as a companion diagnostic to assist with the identification of HRD-positive advanced ovarian cancer.³

Efficacy was established based on PAOLA-1, a double-blind, randomized, placebo-controlled, multicenter trial.² Patients were randomized based on a stratified first-line treatment outcome and tumor BRCAm status that was ascertained by prospective local testing. Retrospective testing was conducted on all available clinical samples using the Myriad myChoice CDx test.³ Patients were randomized (2:1) to receive either 300 mg olaparib orally twice daily combined with bevacizumab 15 mg/kg every 3 weeks (N = 537) or a placebo plus bevacizumab (N = 269). Treatment protocol was for patients to continue receiving bevacizumab in the maintenance setting and to initiate olaparib after a minimum of 3 weeks and up to a maximum of 9 weeks following their last chemotherapy dose. In addition, the patients continued treatment with olaparib for up to 2 years or until disease progressed or toxicity was deemed unacceptable.

Investigator-assessed, progression-free survival (PFS) based on RECIST 1.1 criteria was the major efficacy outcome of the trial. Overall survival was an additional efficacy end point. In the subgroup of patients (N = 387) with HRD-positive tumors, the estimated median PFS was 37.2 months in the olaparib plus bevacizumab arm and 17.7 months in the placebo plus bevacizumab arm. There was consistency between the blinded independent review and the investigator assessment of PFS. However, overall survival data were not considered mature.

Toxicity and adverse events were monitored, with the most common adverse events reported among patients in the olaparib plus bevacizumab cohort being anemia, diarrhea, fatigue (including asthenia), headache, leukopenia, lymphopenia, nausea, neutropenia, urinary tract infection, and vomiting.

Based on the clinical trials, the recommended dose of olaparib is 300 mg taken orally twice daily, with or without food. When combined with olaparib, the recommended dose of bevacizumab is 15 mg/kg intravenously every 3 weeks.

Source

US Food and Drug Administration. FDA approves olaparib plus bevacizumab as maintenance treatment for ovarian, fallopian tube, or primary peritoneal cancers. Published May 8, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary. Accessed March 8, 2021.

References

1. Arora S, Balasubramaniam S, Zhang H, et al. FDA approval summary: olaparib monotherapy or in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer. Oncologist. 2021;26:e164-e172.
2. Lynparza [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; May 2020.
3. GlobeNewswire. Myriad receives FDA approval of myChoice CDx^® as companion diagnostic for Lynparza™ (olaparib) in patients with advanced ovarian cancer. Published May 11, 2020. www.globenewswire.com/news-release/2020/05/11/2030958/0/en/Myriad-Receives-FDA-Approval-of-myChoice-CDx-as-Companion-Diagnostic-for-Lynparza-olaparib-In-Patients-with-Advanced-Ovarian-Cancer.html. Accessed March 8, 2021.