In patients with advanced ovarian cancer, the combination of niraparib (Zejula) plus bevacizumab (Avastin) as maintenance therapy was associated with a progression-free survival (PFS) rate of 89.5% at 6 months, which remained durable to at least 12 months, when the PFS rate was 75%. Median PFS has not yet been reached in patients receiving the combination as part of the single-arm phase 2 OVARIO clinical trial, in which patients received the maintenance combination after first-line platinum-based chemotherapy and bevacizumab.
Furthermore, the combination of niraparib and bevacizumab did not have a cumulative toxic effect. Data from the single-arm phase 2 OVARIO clinical trial indicated that the safety of the combination was consistent with the known side effects of each drug when used as monotherapy, noted Melissa M. Hardesty, MD, Gynecologic Medical Oncologist, Alaska Women’s Cancer Care, Anchorage, at the 2020 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
“As upfront maintenance therapy, our preliminary data suggest that niraparib in combination with bevacizumab is an effective combination to prolong PFS in all biomarker subgroups, consistent with the continuum of clinical benefit observed with monotherapy niraparib maintenance treatment in the PRIMA trial,” reported Dr Hardesty. “Seventy-five percent of women in this trial remain progression-free at 12 months, in a very high-risk population of women.”
Advanced, high-grade serous ovarian cancer typically recurs following primary therapy, generally within the first 1 to 2 years of follow-up.
OVARIO enrolled 105 patients with newly diagnosed with stage IIIB-IV ovarian cancer who had achieved a complete or partial response to first-line platinum-based chemotherapy in combination with bevacizumab. Patients who had cervical debulking were eligible for study entry. At enrollment, all patients underwent tissue testing for homologous recombination (HR) deficiency or proficiency, and 47% were found to have HR deficiency.
Bevacizumab was administered at 15 mg/kg every 3 weeks for up to 15 months. Niraparib was given at a dose of either 300 or 200 mg once daily for up to 3 years, based on baseline body weight and platelet count. Treatment was continued for 3 years or until progressive disease or unacceptable toxicity.
In approximately two-thirds (63%) of patients who received neoadjuvant chemotherapy, 79% had stage III disease and 21% had stage IV, 95% had serous histology, and approximately 40% had only a partial response at the completion of primary therapy, reflecting the high-risk status of the women enrolled, said Dr Hardesty. Most patients (78%) received a starting dose of niraparib at 200 mg.
Among the group of patients with HR deficiency, PFS at 6 months was 98% and 12-month PFS was 88%. Median PFS has still not been reached.
“As has been shown previously with the combination of [poly (ADP-ribose) polymerase] PARP and VEGF inhibition, the incidence of adverse events was high, with almost all patients experiencing some adverse events, and the majority having some grade ≥3 events,” said Dr Hardesty.
No new safety signals were observed. The most common grade ≥3 treatment-related adverse events were thrombocytopenia, anemia, and hypertension.