The FDA has now approved olaparib (Lynparza®, AstraZeneca Pharmaceuticals LP) for maintenance treatment of adults with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer experiencing complete or partial response to first-line platinum-based chemotherapy. Patients are to be selected for therapy using an FDA-approved companion diagnostic, the BRACAnalysis CDx® test (Myriad Genetic Laboratories, Inc.).
The approval was based on the double-blind SOLO-1 trial (NCT01844986), a multi-center study enrolling patients with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer who had already received first-line platinum-based chemotherapy. Patients were randomized 2:1 to receive 300 mg of olaparib twice daily or placebo for up to three years or until objective radiological disease progression. The study's primary efficacy end point was investigator-assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
In 391 patients, olaparib significantly improved PFS compared with placebo. At the time of the data analysis for PFS, estimated median PFS had not been reached in the olaparib arm, compared with 13.8 months in the placebo arm. Data on median overall survival were not yet available.
The recommended dose is 300 mg twice daily, administered orally in sets of two 150-mg tablets, for a total daily dose of 600 mg. Olaparib can be taken with or without food.
"SOLO-1 is truly a landmark trial in gynecologic cancer," commented co-principal investigator Kathleen Moore, MD, Associate Director for Clinical Research at Stephenson Cancer Center at The University of Oklahoma. "This approval will likely change the way we treat women with BRCA-mutated advanced ovarian cancer. 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."
Among patients receiving olaparib in SOLO-1, the most common adverse reactions of any grade, occurring in at least 10% of patients, included nausea, fatigue, abdominal pain, vomiting, anemia, diarrhea, upper respiratory tract infection/influenza/nasopharyngitis/bronchitis, constipation, dysgeusia, decreased appetite, dizziness, neutropenia, dyspepsia, dyspnea, urinary tract infection, leukopenia, thrombocytopenia, and stomatitis.
For More Information
Clinicaltrials.gov (2018). Olaparib maintenance monotherapy in patients with BRCA mutated ovarian cancer following first line platinum based chemotherapy (SOLO-1). NLM identifier: NCT01844986.