By Reuters Staff
NEW YORK (Reuters Health) - 1/10/2019
Adding veliparib to chemotherapy as first-line induction therapy and using it as maintenance therapy significantly prolongs progression-free survival in women with previously untreated stage III or stage IV high-grade serous ovarian carcinoma, a new clinical trial shows.
But in an odd twist, just adding the experimental drug to chemotherapy with carboplatin and paclitaxel did not produce a significant improvement when placebo was substituted for veliparib during maintenance therapy.
The test "shows that the benefit of a PARP inhibitor can be safely extended to all patients with newly diagnosed ovarian cancer," Dr. Robert Coleman of the University of Texas M.D. Anderson Cancer Center in Houston and colleagues write in the New England Journal of Medicine, online September 28. The findings were also presented at the European Society of Medical Oncology Congress in Barcelona.
In the study, financed by AbbVie and known as VELIA/GOG-3005, 1,140 women in 10 countries underwent randomization. Cytoreductive surgery was permitted if performed before the patients began receiving chemotherapy or after three cycles of therapy. Chemotherapy was given for six 21-day cycles and maintenance therapy for 30.
The oral dose of veliparib was 150 mg twice daily during chemotherapy. If the patients didn't have disease progression, they were given maintenance therapy of placebo or 300 mg of veliparib twice daily, which was upped to 400 mg twice daily in the third week.
Among the 26% of patients who had a BRCA mutation, the median progression-free survival was 34.7 months in the veliparib group versus 22.0 months with just chemotherapy and placebo maintenance (P<0.001).
For the 55% who were homologous-recombination deficient (HRD) the rates were 31.9 months and 20.5 months respectively, regardless of BRCA status (also P<0.001).
However, "the independent value of adding veliparib during induction therapy without veliparib maintenance was less clear," Dr. Coleman's team says.
Progression-free survival was actually shorter - although not significantly so - among patients who received veliparib induction therapy but placebo maintenance treatment regardless of BRCA or HRD status.
There were not enough deaths to assess overall survival.
Veliparib did increase the risk of side effects. Rates of thrombocytopenia were 20% among women who received veliparib throughout versus 5% in the control group and 8% among the patients who only got the drug during induction therapy.
A similar pattern was seen with nausea and vomiting. The nausea rate with veliparib given throughout the trial was more than double the rate in the control group.
There was one case each of myelodysplastic syndrome and acute myeloid leukemia in patients who received veliparib.
During the maintenance phase, 19% of veliparib patients discontinued the drug due to an adverse event versus 6% of those receiving placebo. During the induction phase, discontinuation rates were 11% when veliparib was given throughout and 7% in the control group.
N Engl J Med 2019.
Stay up-to-date with Medicom. Subscribe to the Medicom Conference Reports and newsletter.
Medicom provides the highest quality medical information and tools to international medical professionals.