EU Approves Olaparib as Frontline Maintenance for BRCA+ Ovarian Cancer

Dave Fredrickson

Dave Fredrickson

Olaparib (Lynparza) has been approved by the European Commission as a treatment in the maintenance setting for adult patients with advancedBRCA1/2-mutated germline and/or somatic high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response (PR) following frontline treatment with a platinum-based chemotherapy.¹

The approval is based on findings from the double-blind, phase III SOLO-1 trial, in which maintenance olaparib led to a 70% reduction in the risk of disease progression or death compared with placebo in patients withBRCA-mutant advanced ovarian cancer after completing frontline platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41;P<.001).^2,3

The FDA approved olaparib for this indication in December 2018.

&ldquo;This approval sets the stage for a new standard of care in the [European Union] for women with advanced ovarian cancer and aBRCAmutation,&rdquo; Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, which co-develops olaparib with Merck, stated in a press release. &ldquo;The goals of frontline therapy have always been long-term remission and even cure, yet currently 70% of patients relapse within three years of initial treatment. The progression-free survival benefit of Lynparza observed in SOLO-1 represents a major step forward in our ambition to help improve patient outcomes.&rdquo;

In the phase III SOLO-1 trial, maintenance olaparib following platinum-based chemotherapy was evaluated in newly diagnosed patients with advanced ovarian cancer with aBRCA1/2mutation. Patients with newly diagnosed, FIGO stage III/IV, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations. The patients must have also undergone cytoreductive surgery, and be in clinical complete response or PR following platinum-based chemotherapy.

Treatment was continued until disease progression, and was ceased for patients with no evidence of disease at 2 years. However, patients with a PR at 2 years could continue therapy.

The primary endpoint was progression-free survival (PFS). Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.

At a median follow-up of 41 months, results showed that the median PFS by independent central review was not reached in the olaparib arm (n = 260), versus 14.1 months in the placebo arm (n = 131). The investigator-assessed PFS in the olaparib arm was not reached, compared with 13.8 months in the placebo arm.

Additionally, patients who received olaparib maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72;P= .0002). Overall survival data are not yet mature. There were no clinically relevant changes in quality of life (QoL). Moreover, the discontinuation rate in the olaparib arm was 12%.

Regarding safety, adverse events observed were low-grade, with the most common grade &ge;3 AEs in the olaparib arm being anemia (22%) and neutropenia (8%). Baseline characteristics, including health-related quality-of-life scores, were balanced between the 2 arms.

Additional trials, such as the ongoing phase III PAOLA-1 study, is testing the combination of olaparib and bevacizumab (Avastin) as a first-line maintenance treatment for patients with advanced, stage IIIB-IV high-grade serous or endometrioid, fallopian tube, or peritoneal ovarian cancer, regardless ofBRCAstatus.

Previously, olaparib was approved in Europe for the maintenance treatment of patients with platinum-sensitive, relapsed ovarian cancer, regardless ofBRCAmutation status. It is approved in the United States as first-line maintenance treatment inBRCA-mutant advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 38 countries, including the United States, countries in the European Union and Japan, for germlineBRCA-mutant HER2-negative metastatic breast cancer who were previously treated with chemotherapy; this includes locally advanced breast cancer in the European Union.

References:

1. LYNPARZA&reg; (olaparib) Approved in the EU for Use as First-Line Maintenance Therapy in Patients WithBRCA-Mutated Advanced Ovarian Cancer. Merck. Published June 18, 2019. https://bit.ly/2KpmY3o. Accessed June 18, 2019.
2. Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III—IV ovarian cancer (OC) with aBRCA1/2mutation (BRCAm): phase III SOLO1 trial. Presented at: 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.
3. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer.N Eng J Med. 2018;379(26):2495-2505. doi: 10.1056/NEJMoa1810858.