Olaparib plus bevacizumab for ovarian cancer maintenance therapy

1. This phase 3 trial of olaparib plus bevacizumab showed a significant progression-free survival benefit for ovarian cancer maintenance therapy.

2. The progression-free survival benefit was greater in patients with BRCA-positive and homologous recombination deficiency (HRD) positive tumors.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Due to the late diagnosis of advanced-stage ovarian cancer, a majority of patients experience a relapse after 10 to 18 months, even after treatment with surgery and chemotherapy. Current maintenance therapy includes the option of bevacizumab alone. Upcoming trials are exploring PARP (polyadenosine diphosphate-ribose polymerase) inhibitors which target tumors with homologous-recombination deficiency (HRD), present in about 50% of high-grade serous ovarian tumors. This randomized phase 3 trial of olaparib, a PARP inhibitor, explored the effects of olaparib plus bevacizumab on progression-free survival. Participants with newly diagnosed, advanced, high-grade ovarian cancer were assigned in a 2:1 ratio to either receive olaparib at a dose of 300mg twice daily) or placebo between 3 to 9 weeks after the last chemotherapy.. Olaparib plus bevacizumab had an overall median progression-free survival of 22.1 months, as compared to 16.6 months with placebo plus bevacizumab. Disease progression and death rates were lower for those with BRCA-positive and HRD-positive tumors. Olaparib plus bevacizumab offered increased survival and decrease in relapse, especially in those with BRCA-positive and HRD-positive tumors. Future research should focus on determining long-term effects of this drug combination.

Click to read the study in NEJM

Relevant Reading: Olaparib in the treatment of ovarian cancer

In-Depth [randomized controlled trial]: This randomized phase 3 trial was conducted in 11 countries from 2015 to 2017, with data collected up to March 2019. 806 participants aged 18 years and older with newly diagnosed, advanced, high-grade ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer with response to platinum-taxane chemotherapy plus bevacizumab treatment were included in this study. Patients were followed to determine disease progression with imaging or until death. Overall progression-free survival was 22.1 months in the olaparib group versus 16.6 months in the placebo group (hazard ratio for disease progression or death, 0.59; 95% CI, 0.49 to 0.72; P<0.001). Patients with BRCA-positive tumors had a median progression-free survival of 37.2 months in the olaparib group and 21.7 months in the placebo group (hazard ratio for disease progression or death, 0.31; 95% CI, 0.20 to 0.47). Those with BRCA-negative tumors had a median progression-free survival of about 17 months. Patients with HRD-positive tumors had a median progression-free survival of 37.2 months in the olaparib group and 17.7 months in the placebo group (hazard ratio for disease progression or death, 0.33; 95% CI, 0.25 to 0.45). Those with HRD-negative tumors had a median progression-free survival of 16 months. The most common adverse effects in the intervention group was nausea, fatigue, anemia, and lymphopenia.

Image: PD

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