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Substantial Benefit with Addition of Olaparib to Bevacizumab Maintenance in Newly Diagnosed Advanced Ovarian Cancer

Conference Correspondent

Compared with bevacizumab and placebo, frontline maintenance therapy with olaparib plus bevacizumab reduced the risk of progression by 41% overall, and by 69% in the BRCA-mutated subset in women with newly diagnosed ovarian cancer, according to data from the phase 3 PAOLA-1 trial, presented by lead investigator Isabelle Ray-Coquard, MD, PhD, at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

“The median progression-free survival (PFS) increased from almost 17 months in the bevacizumab arm up to 22 months in the combination arm,” she 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.”

PAOLA-1 is the first phase 3 trial to evaluate maintenance therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor in patients with advanced ovarian cancer—regardless of BRCA mutation status—who were responding to first-line standard-of-care treatment with chemotherapy plus bevacizumab. “As we know, bevacizumab prolongs PFS and also overall survival in some high-risk subgroups,” she noted.

The PAOLA-1 trial 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 prior platinum-based chemotherapy and bevacizumab for at least 3 cycles and responded to treatment.

Patient characteristics were well-balanced between the study arms; the majority of patients had good performance status, ovarian primary tumor localization with serous histology, and FIGO stage III disease. Close to 50% of patients were homologous recombination deficiency (HRD)-positive, and 29% of patients had BRCA-mutated tumors. Outcomes were evaluated according to HRD and tumor BRCA mutation status.

PAOLA-1 met its primary end point of a statistically significant improvement in PFS in the intent-to-treat population. Maintenance therapy with the treatment combination improved median PFS from 16.6 months to 22.1 months (hazard ratio [HR], 0.59; P <.0001) in the overall population, regardless of BRCA mutation status.

While all patient subsets benefited, median PFS was longest among patients with HRD-positive tumors, including those that had BRCA mutations: 37.2 months with combination treatment compared with 17.7 months with placebo (HR, 0.33). Patients with HRD-positive tumors that did not have BRCA mutations also experienced a substantial PFS benefit with the addition of olaparib to bevacizumab, with a median PFS improvement of almost 1 year: 28.1 months versus 16.6 months (HR, 0.43).

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

“However, the median PFS of 16 months in the control arm is close to what we observed in the HRD-positive population, and suggests efficacy of bevacizumab in the HRD-negative population,” she noted.

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 impact on bevacizumab tolerability. Dose modifications and discontinuations were more frequent in the olaparib arm; however, no differences were observed in health-related quality of life between arms.


  • SGO 2020 Annual Meeting on Women’s Cancer. Abstract 33. Presented April 29, 2020.

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