Treatment with niraparib and bevacizumab does not appear to have a cumulative toxic effect in patients with advanced ovarian cancer who responded to first-line platinum-based chemotherapy and bevacizumab; the safety of the drug combination was consistent with the known side effects of each drug as monotherapy. Median progression-free survival (PFS) has not yet been reached in patients receiving the combination after first-line platinum-based chemotherapy and bevacizumab. These findings come from the single-arm phase 2 OVARIO trial, presented by Melissa M. Hardesty, MD, at the Society of Gynecologic Oncology (SGO) 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, a specialist in gynecologic medical oncology at Alaska Women’s Cancer Care. “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. “The use of tolerable maintenance therapy to prevent or delay this recurrence has been a long sought-after goal,” she said.
When administered after platinum-based chemotherapy, niraparib is known to improve PFS in all important subgroups of patients with newly diagnosed and recurrent ovarian cancer. To be eligible for the study, patients were newly diagnosed with FIGO stage IIIB-IV ovarian cancer and had demonstrated a complete or partial response to first-line platinum-based chemotherapy in combination with bevacizumab. Patients receiving neoadjuvant chemotherapy, as well as primary debulking surgery, were eligible. “But an attempt at cervical debulking was required,” she noted. At enrollment, all patients underwent tissue testing for homologous recombination deficiency or proficiency.
Bevacizumab was administered at a dose of 15 mg/kg every 3 weeks for up to 15 months, including time on first-line chemotherapy. 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. Administration was started within 12 weeks of completing first-line treatment and continued for 3 years, or until progressive disease or unacceptable toxicity.
The study’s primary end point is a “landmark” PFS at 18 months from treatment initiation, and an interim analysis of PFS at 6 months from treatment initiation was performed after all patients had had 2 scans following initiation of treatment. At SGO, Dr Hardesty reported the landmark 6- and 12-month PFS rates.
The study enrolled 105 patients with a median age of 60 years and a median body weight of 68 kg. The majority of patients received neoadjuvant chemotherapy (63%), were stage III (79%), and had serous histology (95%).
Overall, approximately half of patients had preexisting hypertension, and 47% of patients were homologous recombination deficient (HRD), including BRCA-mutated and BRCA wild-type. Most patients (78%) received a starting dose of niraparib at 200 mg.
“I would like to point out that this population of women was a very high-risk population, as evidenced by the fact that 63% were treated with neoadjuvant chemotherapy, 21% had stage IV disease, and almost 40% had only a partial response at the completion of primary therapy,” she said. “This distribution of high-risk markers is similar to that seen in the PRIMA trial, and is even higher than the proportion of neoadjuvant chemotherapy reported in PAOLA; there were more women with only a partial response to primary therapy as well.”
At 6 months, the PFS rate was 90%, and at 12 months, PFS was 75%. Among the HRD group, 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 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.
Overall, no new safety signals were observed. Dose interruptions and reductions were common, but only 25% led to treatment discontinuation. The most common grade ≥3 treatment-related adverse events were thrombocytopenia, anemia, and hypertension. According to the investigators, this side-effect profile is similar to that seen in the AVANOVA trial, which used the same drug combination.
- SGO 2020 Annual Meeting on Women’s Cancer. Abstract 4. Presented May 14, 2020.