(Reuters Health) – Women with newly diagnosed ovarian cancer and a BRCA mutation see sustained benefits in progression free survival rates after two years of maintenance olaparib therapy, a clinical trial analysis suggests.
The study focused on women with BRCA mutations and newly-diagnosed advanced high grade serous or endometrioid ovarian cancer who had a complete or partial clinical response to platinum-based chemotherapy. They randomized women 2:1 to receive olaparib 300 mg twice daily (n=260) or placebo (n=131) maintenance therapy for two years.
Progression-free survival was significantly shorter with placebo than with olaparib (hazard ratio 0.33), researchers report in The Lancet Oncology.
The median follow-up period with olaparib was 4.8 years and median progression-free survival was 56 months. That compares with a median follow-up period of 5.0 years and median progression-free survival of 13.8 months with placebo.
“The extent of sustained benefit beyond 2 years of olaparib seen in the 5 year follow up analysis provides proof of principle that patients with no visible cancer can continue to benefit after stopping 2 years of olaparib,” said lead study author Dr. Susana Banerjee of the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research in London.
“The magnitude of benefit is what we all would hope for and great to see,” Dr. Banerjee said by email.
The majority of patients in the trial had BRCA1 mutations (72%), while 106 (27%) had BRCA2 mutations and three (1%) had both mutations.
Median intervention duration was 24.6 months with olaparib and 13.9 months with placebo. There were 123 patients (47%) on olaparib and 92 patients (71%) on placebo who discontinued the intervention before the two-year point targeted by the study design.
In an analysis of the secondary efficacy outcome of time to second disease progression or death, five-year progression free survival was 64% with olaparib and 41% with placebo.
Anemia was the most common grade 3 or worse adverse event among patients with olaparib (22% vs 2% with placebo), followed by neutropenia (8% vs 5%), and fatigue or asthenia (4% vs 2%).
Serious adverse events happened more often with olaparib (21%) than with placebo (13%), as did treatment-related serious adverse events (10% vs 2%).
There were no new safety signals in the trial that hadn’t been seen in previous olaparib studies, the researchers note. There also were no additional cases of myelodysplastic syndrome or acute myeloid leukemia reported, beyond what had been identified in earlier studies.
Overall survival data were not yet available.
Even so, the results suggest that all women with newly-diagnosed advanced ovarian cancer and a BRCA mutation should be considered for maintenance olaparib after surgery and a response to platinum-based chemotherapy, Dr. Banerjee said.
“The reasons are clear – more women living without cancer returning,” Banerjee said. “This raises the possibility that more women could potentially be cured, and we are awaiting overall survival analysis.”
SOURCE: https://bit.ly/32x0DuX The Lancet Oncology, online October 26, 2021.