Addition of olaparib to maintenance bevacizumab significantly improves PFS in ovarian cancer
BARCELONA, Spain — The addition of olaparib to bevacizumab maintenance therapy after first-line platinum-based chemotherapy and bevacizumab significantly improved PFS among women with advanced ovarian cancer, according to results of the randomized phase 3 PAOLA-1/ENGOT-ov25 study presented at European Society for Medical Oncology Congress.
The PFS benefit appeared particularly substantial among women with BRCA mutations and those with homologous recombination deficiency-positive disease, researchers noted.
“Bevacizumab increased response rates, PFS, and OS in some subgroups, so it is a standard-of-care for most patients with newly advanced ovarian cancer,” Isabelle L. Ray-Coquard, MD, PhD, medical oncologist in the medical oncology department and Institute for Clinical Science at Centre Leon Berard in France and professor of medical oncology at University Claude Bernard Lyon I, said during her presentation. “This is the first randomized trial to explore the efficacy and safety of the combination of olaparib and bevacizumab [for] patients with newly-advanced ovarian cancer.”
The study by Ray-Coquard and colleagues included 806 women with stage III or stage IV high-grade serous or endometrioid ovarian, fallopian tube or primary peritoneal cancer who were in clinical complete or partial response after receiving standard platinum-based chemotherapy in combination with bevacizumab (Avastin, Genentech).
Researchers randomly assigned the women 2:1 to maintenance bevacizumab with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza, AstraZeneca; n = 537) or with placebo (n = 269).
Researchers administered olaparib at 300 mg orally for up to 24 months and bevacizumab at 15 mg/kg for 15 months.
PFS in the intent-to-treat population served as the study’s primary endpoint.
Median follow-up was 24 months in the olaparib group and 22.7 months in the placebo group.
Results showed significantly longer median PFS in the olaparib group compared with the placebo group (22.1 months vs. 16.6 months; HR = 0.59; 95% CI, 0.49-0.72).
Among patients with BRCA-mutated tumors, median PFS was 37.2 months in the olaparib group vs. 21.7 months in the placebo group (HR = 0.31; 95% CI, 0.2-0.47). Among women without BRCA mutations, median PFS was 18.9 months in the olaparib group vs. 16 months in the placebo group (HR = 0.71; 95% CI, 0.58-0.88).
Women with homologous recombination deficiency (HRD)-positive disease had median PFS of 37.2 months with olaparib vs. 17.7 months with placebo (HR = 0.33; 95% CI, 0.25-0.45). Women with HRD-positive status without BRCA mutations had median PFS of 28.1 months with olaparib and 16.6 months with placebo group. Women with HRD-negative or unknown status had median PFS of 16.9 months with olaparib and 16 months with placebo.
“It is interesting to note that PFS in the combination arm is longer than what was seen in the SOLO-1 trial, which is probably due to the use of bevacizumab,” Ray-Coquard said.
Grade 3 or higher adverse events occurred among 57% of women in the olaparib group and 51% of patients in the placebo group. More than half of the women in the olaparib group (54%) had dose interruptions because of adverse events, compared with 24% in the placebo group.
“[This study] population is representative of the majority of patients with advanced ovarian cancer [because] patient selection was not restricted by surgical outcome or BRCA mutation status,” Ray-Coquard said. “I can also tell you that the safety profile of olaparib in combination with bevacizumab was generally consistent with previous trials and the addition of olaparib did not have an impact on bevacizumab tolerability and quality-of-life.”– by John DeRosier
Ray-Coquard IL, et al. Abstract LBA2_PR. Presented at: European Society for Medical Oncology Congress; Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosures: Arcagy, AstraZeneca and Roche funded this study. Ray-Coquard reports consultant roles with and honoraria from AstraZeneca, Clovis Oncology, Pharma Mar and Tesaro; travel expenses from AstraZeneca and Roche; research funding from Merck Sharpe & Dohme; and a consultant role with Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.