Cediranib plus olaparib effective, safe for recurrent, platinum-resistant ovarian cancer
BARCELONA, Spain — The combination of cediranib and olaparib appeared to be effective and safe for women with heavily pretreated, platinum-resistant ovarian cancer, according to results of a randomized phase 2 study presented at European Society for Medical Oncology Congress.
Administration of this regimen in a continuous dosing schedule also may improve PFS among women with BRCA wild-type disease compared with weekly paclitaxel, researchers noted.
“Platinum-resistant ovarian cancer still represents a high unmet need,” Nicoletta Colombo, MD, assistant professor of obstetrics and gynecology at University of Milan-Bicocca in Italy, said during her presentation. “Currently, median PFS for these patients is 3 to 4 months even after weekly paclitaxel, which is recognized as the most effective chemotherapy regimen. New therapeutic options in this setting would be of great clinical interest.”
A previous study showed cediranib (AZD2171, AstraZeneca) in combination with olaparib (Lynparza, AstraZeneca) improved PFS for women with recurrent, platinum-sensitive ovarian cancer compared with olaparib alone.
In the current study, researchers randomly assigned 123 women with platinum-resistant ovarian cancer to receive paclitaxel at 80 mg/m2 once weekly for 24 weeks (control group; n = 41), olaparib at 300 mg twice daily with cediranib at 20 mg daily (continuous group; n = 41), or olaparib at 300 mg twice daily with cediranib 5 days a week (intermittent group; n = 41).
PFS served as the primary endpoint.
Results showed continuous cediranib and olaparib conferred superior median PFS (5.7 months) compared with intermittent cediranib and olaparib (3.8 months) and paclitaxel (3.1 months).
The estimated HR for PFS in the continuous group vs. the control group was 0.76 (90% CI, 0.49-1.17). Estimated HR for PFS in the intermittent group vs. the control group was 1.08 (90% CI, 0.71-1.64).
For the subgroup of women with germline BRCA wild-type disease, median PFS in the continuous group (5.8 months; range, 3.8-8.7) was superior to that of the intermittent group (3.8 months; range, 2-5.8) and the paclitaxel group (2.1 months; range, 1.9-6.7). Among these women, the HR for PFS in the continuous therapy vs. the paclitaxel group was 0.63 (95% CI, 0.36-1.1), and the HR for PFS in the intermittent group vs. the paclitaxel group was 0.96 (95% CI, 0.57-1.62).
One treatment-related death due to myelodysplastic syndrome occurred in the continuous group, and one treatment-related death due to sepsis occurred in the paclitaxel group.
Common adverse events across all groups included fatigue and anemia. Diarrhea and nausea were common in the continuous and intermittent groups.
“Although not statistically significant, the continuous administration shows a promising trend for improved PFS, particularly in the germline BRCA wild-type population,” Colombo said. “The combination of cediranib and olaparib represents an active, feasible oral regimen [that] deserves further investigation.” – by John DeRosier
Colombo N, et al. Abstract 2560. Presented at: European Society for Medical Oncology Congress. Sept. 27-Oct. 1, 2019; Barcelona, Spain.
Disclosure: AstraZeneca funded this study. Colombo reports consultant roles and honoraria with AstraZeneca, Genentech/Roche, PharmaMar and Tesaro, and consultant roles with BioCad, Clovis Oncology, Merck Sharp & Dohme, Pfizer and Takeda. Please see the abstract for all other authors’ relevant financial disclosures.