FDA Approves Olaparib for Frontline Maintenance in Ovarian Cancer

The FDA has approved olaparib (Lynparza) as a maintenance treatment for 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 frontline platinum-based chemotherapy, as approved by an FDA-approved companion diagnostic assay. This is the first approval for a PARP inhibitor in the first-line maintenance setting.

The agency also approved BRACAnalysis CDx^® to be used by healthcare professionals to identify patients with advanced ovarian cancer who have a germline BRCA mutation and are eligible for first-line maintenance therapy with olaparib in this setting.

The olaparib approval is based off of findings from the phase III SOLO-1 trial, in which olaparib reduced the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001) compared with placebo following platinum-based chemotherapy. Olaparib’s safety profile was consistent with previous trials.

“SOLO-1 is truly a landmark trial in gynecologic cancer. This approval will likely change the way we treat women with BRCA-mutated advanced ovarian cancer,” said Kathleen Moore, co-principal investigator of the SOLO-1 trial and associate director for Clinical Research, Stephenson Cancer Center at The University of Oklahoma, in a press release. “The ability to offer this important first-line maintenance treatment option to eligible patients may slow down or even stop the natural course of disease progression.”

The phase III SOLO-1 trial evaluated maintenance olaparib following platinum-based chemotherapy in newly diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. 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 were enrolled. These patients must have also received cytoreductive surgery, and be in clinical complete response or partial response after platinum-based chemotherapy.

The study treatment in SOLO-1 continued until disease progression, and treatment was ceased for patients with no evidence of disease at 2 years. However, patients with a partial response at 2 years could continue treatment.

Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.

Results showed that, at a median follow-up of 41 months, the median progression-free survival (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 (HR, 0.30; 95% CI, 0.23-0.41; P <.0001). The median PFS for olaparib has not yet been reached.

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. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the olaparib arm was 12%.

Adverse events observed were low-grade, with the most common grade ≥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.

“Women with ovarian cancer are often first diagnosed with advanced disease, which is associated with poor outcomes,” said Dave Fredrickson, executive vice president, head, Oncology Business Unit, AstraZeneca, in the press release. “In SOLO-1, Lynparxa in the first-line maintenance setting reduced the risk of disease progression or death by 70% for patients with BRCA-mutant advanced ovarian cancer. Today’s approval is a critical advancement and brings us closer to our goal of helping these patients achieve long-term remission.”

References

1. 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 a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.
2. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer [published online ahead of print on October 21, 2018]. N Eng J Med. doi: 10.1056/NEJMoa1810858.