When used after response to first-line platinum-based chemotherapy plus bevacizumab (Avastin) in women with high-grade serous ovarian cancer, the combination of niraparib (Zejula) and bevacizumab induced a 6-month progression-free survival (PFS) of 89.5% in an interim analysis of the phase 2 OVARIO study. In addition, the combination did not cause cumulative toxicities in the single-arm study, announced Melissa M. Hardesty, MD, Gynecologic Medical Oncology Specialist, Alaska Women’s Cancer Care, Anchorage, at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
The primary end point of OVARIO is PFS at 18 months from treatment initiation.
“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 often recurs following primary therapy, generally within the first 1 to 2 years of follow-up. “The use of tolerable maintenance therapy to prevent or delay this recurrence has been a long sought-after goal,” she said.
OVARIO includes 105 patients (median age, 60 years) with newly diagnosed International Federation of Gynecology and Obstetrics stage IIIB-IV ovarian cancer who had a complete response or partial response after first-line platinum-based chemotherapy plus bevacizumab. Approximately half (47%) of patients had homologous recombination deficiency (HRD) on tissue testing at enrollment.
Patients were treated with bevacizumab 15 mg/kg every 3 weeks for up to 15 months. Niraparib was dosed at 300 or 200 mg once daily, based on baseline body weight and platelet count, starting within 12 weeks of completing first-line treatment and continued for 3 years or until progressive disease or unacceptable toxicity. The starting niraparib dosage was 200 mg in 78% of patients.
The population was high-risk, as evidenced by the use of neoadjuvant chemotherapy in 63% and the presence of stage IV disease in 21%, said Dr Hardesty. Almost 40% had only a partial response at the completion of primary therapy.
The PFS rate at 12 months was 75%. Median PFS has still not been reached. Among the patients with HRD, PFS rates were 98% at 6 months and 88% at 12 months.
No new safety signals were observed. Dose interruptions and reductions were common, but only 25% led to treatment discontinuation.
“As has been shown previously with the combination of 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. The most common grade ≥3 treatment-related adverse events were thrombocytopenia, anemia, and hypertension, similar to that seen in the AVANOVA trial, which used the same drug combination, she noted.