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Adding Olaparib to Bevacizumab as Maintenance Extends PFS in Newly Diagnosed Advanced Ovarian Cancer

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Frontline maintenance therapy with olaparib (Lynparza) added to bevacizumab (Avastin) reduced the risk for disease progression compared with placebo plus bevacizumab in women with newly diagnosed ovarian cancer.

Data from the PAOLA-1 clinical trial, a phase 3 trial evaluating maintenance therapy with a poly (ADP-ribose) polymerase inhibitor in patients with advanced ovarian cancer regardless of BRCA mutation status, also demonstrated a greater advantage to the olaparib plus bevacizumab maintenance combination on progression-free survival (PFS) in the subset of women with BRCA-mutated ovarian cancer than in the overall study population, reported Isabelle Ray-Coquard, MD, PhD, Medical Oncologist, Institute for Clinical Science, Centre Leon Bérard, Lyon, France, at the 2020 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.

In the overall study cohort, regardless of BRCA mutation status, median PFS increased from 16.6 months in the placebo plus bevacizumab arm to 22.1 months in the olaparib plus bevacizumab arm, an improvement of 41% (hazard ratio [HR], 0.59; P <.0001), Dr Ray-Coquard reported. “We have to note that patients started first-line treatment a median of 7 months before randomization, so patients in this trial receiving chemotherapy and bevacizumab plus olaparib experienced a total median time without progression of almost 30 months.”

The magnitude of benefit with olaparib was greatest among patients whose tumors tested positive for BRCA1/2 mutations, with a median PFS of 37.2 months in the olaparib plus bevacizumab arm compared with 21.7 months in the placebo arm (HR, 0.31; 95% confidence interval [CI], 0.20-0.47).

Approximately 50% of patients in PAOLA-1 trial were homologous recombination deficiency (HRD)-positive, and 29% of patients had BRCA-mutated tumors.

In patients with HRD-positive tumors, including tumors that had BRCA mutations, the median PFS was 37.2 months in the olaparib arm versus 17.7 months in the placebo arm (HR, 0.33; 95% CI, 0.25-0.45).

In patients with HRD-positive tumors that did not have BRCA mutations, the median PFS was 28.1 months in the olaparib arm versus 16.6 months in the placebo arm (HR, 0.43; 95% CI, 0.28-0.66).

PAOLA-1 enrolled 806 women with newly diagnosed stage III or IV high-grade serous or endometroid ovarian, fallopian tube, or primary peritoneal cancer. Patients were randomized 2:1 to receive olaparib (300 mg twice daily for up to 2 years) plus bevacizumab (15 mg/kg every 3 weeks for 15 months), or placebo. Patient eligibility was not restricted by surgical outcome or BRCA mutation status. All patients had received previous platinum-based chemotherapy and bevacizumab for at least 3 cycles and responded to treatment.

There was no significant difference in PFS between the 2 arms for patients who were HRD-negative or who had an unknown HRD status.

The safety profile of olaparib in combination with bevacizumab was generally consistent with previous trials of each drug, and the addition of olaparib did not affect tolerability of bevacizumab. Dose modifications and discontinuations were more frequent in the olaparib arm; however, no differences were observed in health-related quality of life between arms.

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