Zejula (niraparib) given in combination with Avastin (bevacizumab) shows promising safety and efficacy at delaying disease progression in women with advanced ovarian cancer who had responded to a first-line platinum-based chemotherapy plus Avastin, interim results from a Phase 2 trial show.
These findings are in the presentation, “Phase II OVARIO study of niraparib + bevacizumab therapy in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab,” for the May 14 webinar as part of the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer. The meeting, set for March in Toronto, was canceled due to the COVID-19 pandemic.
Avastin, developed by Genentech (part of the Roche Group), belongs to a class of medications known as anti-angiogenic therapies. It works by stopping tumors from making their own blood vessels, thereby limiting cancer growth.
Zejula is an oral PARP inhibitor marketed by Tesaro, a subsidiary of GlaxoSmithKline. It works by blocking the activity of PARP enzymes, which are involved in DNA repair. By inhibiting these enzymes, Zejula prevents cancer cells from repairing their DNA, eventually leading to their death.
It enrolled 105 women (median age of 60) with advanced ovarian cancer who had responded to first-line treatment with platinum-based chemotherapy in combination with Avastin.
During the trial, participants received Avastin at a dose of 15 mg/kg, administered intravenously (into the bloodstream) every three weeks for up to 15 months, including time on the first-line chemotherapy. Zejula was given orally, once daily, at a dose of 200 or 300 mg depending on a patient’s body weight and platelet count.
Treatment with Zejula was started within 12 weeks of patients finishing their first-line treatment, and continued for a period of three years or until patients showed signs of disease progression or unacceptable toxicity.
The study’s main goal was to assess the efficacy of this combination at delaying disease progression or death — a measure known as progression-free survival, or PFS — at 18 months after treatment initiation.
Most patients had serous ovarian cancer (95%) determined to be at stage 3 (or locally advanced; 79%). Nearly half (47%) of the women had mutations in certain genes involved in DNA repair and/or genomic instability (a high frequency of mutations within the genome). This status is known as “homologous recombination deficiency” (HRd).
A preliminary analysis done six months after starting the combo therapy showed that 89.5% of these women had no signs of disease progression. The trial is expected to end in November 2021.
“Median PFS in advanced OC [ovarian cancer] following first-line platinum-based chemotherapy + bevacizumab [Avastin] has not been reached,” the researchers wrote.
The combination’s safety profile was consistent with that of either therapy when used alone.
Severe (grade 3), life-threatening (grade 4), or fatal (grade 5) treatment-emergent adverse events included thrombocytopenia (low platelet counts), anemia, and high blood pressure. These events were similar to those reported in a Phase 1/2 trial (NCT02354131), called AVANOVA, which evaluated the same combo therapy in ovarian cancer patients.
“Safety of the niraparib [Zejula] + bevacizumab [Avastin] combination was consistent with the known side effects of each drug as monotherapy, and the combination did not appear to cause cumulative toxicities,” the researchers wrote.
Zejula’s use was extended by the FDA last month to include that of a first-line maintenance monotherapy for women with advanced ovarian cancer who responded to platinum-based chemotherapy, regardless of BRCA mutation status. It is also approved in the U.S. as a maintenance therapy for recurrent ovarian cancer that responded to platinum-based chemotherapy, and as a late-line therapy for tumors positive for HRd.