Olaparib (Lynparza®, AstraZeneca Pharmaceuticals, LP), in combination with bevacizumab (Avastsin®, Genentech), is now FDA approved as first-line maintenance treatment for adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have had a complete or partial response to first-line platinum-based chemotherapy. Patients must also have cancer that is associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA mutation and/or genomic instability. A companion diagnostic, Myriad myChoice® CDx (Myriad Genetic Laboratories, Inc.), for olaparib was also FDA approved.
Previously approved for advanced ovarian cancer, metastatic breast cancer, and metastatic pancreatic cancer, olaparib targets and inhibits PARP, a protein that repairs DNA damage in cancer cells to help them survive. In addition to this recent approval, bevacizumab is indicated for epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel for stage III or IV disease after initial surgical resection. Bevacizumab starves cancer cells by blocking blood vessels from reaching them.
Approval was based on efficacy shown in a randomized, double-blind, placebo-controlled, multi-center trial, PAOLA-1 (NCT02477644). The study enrolled 806 patients with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer who have previously received first-line platinum-based chemotherapy and bevacizumab.
In a randomized 2:1 ratio, patients received either 300 mg of olaparib, to be taken orally twice daily plus bevacizumab or placebo in combination with bevacizumab. In the maintenance setting, participants continued bevacizumab and started olaparib after a minimum of 3 weeks up to a maximum of 9 weeks after receiving their last chemotherapy dose. For up to 2 years, olaparib was administered unless disease progression or unacceptable toxicity occurred.
Among 387 patients with HRD-positive tumors, an increased median progression-free survival was observed in the olaparib group compared with the placebo group (37.2 vs 17.7 months). Olaparib with bevacizumab was associated with nausea, fatigue, anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache.
Per recommendation, olaparib is to be taken orally twice daily at a dose of 300 mg, on a full or empty stomach. The recommended bevacizumab dose when taken with olaparib is 15 mg/kg intravenously every 3 weeks.
For More Information
Avastin® (bevacizumab) prescribing information (2020). Genentech. Available at: https://www.avastin.com/
Lynparza® (olaparib) prescribing information (2020). AstraZeneca. Available at: https://www.lynparza.com/
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