FDA has expanded the indication of Lynparza (olaparib) to include its combination with bevacizumab for first-line maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
The combination is indicated for adult patients with complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability.
Lynparza is sponsored by AstraZeneca. Myriad myChoice CDx (Myriad Genetic Laboratories Inc.) was approved as a companion diagnostic for olaparib.
Efficacy of this new indication was investigated in PAOLA-1, a randomized, double-blind, placebo-controlled, multi-center trial comparing olaparib with bevacizumab versus placebo plus bevacizumab in patients with advanced high-grade epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab. Randomization was stratified by first-line treatment outcome and tumor BRCA mutation status, determined by prospective local testing. All available clinical samples were retrospectively tested with Myriad myChoice CDX test.
Patients were randomized (2:1) to receive olaparib tablets 300 mg orally twice daily in combination with bevacizumab (n=537) 15 mg/kg every three weeks or placebo plus bevacizumab (n=269). Patients continued bevacizumab in the maintenance setting and started olaparib after a minimum of 3 weeks and up to a maximum of 9 weeks following their last chemotherapy dose. Olaparib was continued for up to 2 years or until disease progression or unacceptable toxicity.
The major efficacy outcome measure was investigator-assessed progression-free survival evaluated according to RECIST 1.1. An additional efficacy endpoint was overall survival. Estimated median PFS in the subgroup of 387 patients with HRD-positive tumors was 37.2 months in the olaparib with bevacizumab arm and 17.7 months in the placebo plus bevacizumab arm (HR 0.33; 95% CI: 0.25-0.45). Results from a blinded independent review of PFS were consistent with the investigator-assessed PFS analysis. OS data were not mature.
