Ovarian Cancer Canada’s research initiatives employ a bench-to-bedside approach to drive transformative change in outcomes for those diagnosed with this disease. Two funded clinical trials, though different in their approach and focus, share a dedication to exploring innovative treatment pathways and a made-in-Canada pedigree.
The emergence of PARP (poly-ADP ribose polymerase) inhibitors as a maintenance drug was a significant breakthrough for individuals who had undergone chemotherapy treatment for high-grade serous ovarian cancer (HGSC). Now, a new clinical trial is exploring the efficacy of placing PARP inhibitors in the front line – prior to chemotherapy or surgery – as part of a three-drug treatment for individuals with stage 4 HGSC. Led by B.C. Cancer Medical Oncologist Dr. Yvette Drew, the Neoadjuvant Olaparib Combination Ovarian Cancer Targeted Study (NEOCATS) aims to improve outcomes through a treatment regimen that combines the PARP inhibitor Olaparib and the immunotherapy treatment Durvalumab with Bevacizumab, a drug that blocks and interferes with the cancer’s blood supply.
If it is successful, it could ultimately lead to a complete paradigm shift in how we treat high-grade serous ovarian cancer.
“This clinical trial uses a combined approach to ‘target the targets’ within the cancer cells from the very beginning of a patient’s treatment journey, rather than treating with chemo first,” says Alicia Tone, PhD, OvCAN Project Manager & Scientific Advisor, Ovarian Cancer Canada. “If it is successful, it could ultimately lead to a complete paradigm shift in how we treat high-grade serous ovarian cancer.” For individuals with stage 4 HGSC, the benefit of a treatment strategy using up-front chemotherapy, followed by surgery is small; many individuals experience a return of the cancer in as little as one year. Shifting PARP inhibitors, in combination with two other drugs, to the front line is by all accounts innovative. NEOCATS is only the second trial to investigate the promise of this “targeting the targets” approach, and the first to focus solely on ovarian cancer.
“A lot of ovarian cancer patients are treated with chemotherapy and surgery, and the dogma is that chemotherapy is very effective in individuals with high-grade serous cancer,” Tone explains. “This is true overall except in the population of individuals that is in this trial, stage 4 high-grade serous ovarian cancer patients. They need better treatment; the standard of care of chemotherapy followed by surgery for stage 4 high-grade serous patients is actually not the gold standard. We need a new gold standard.”
The NEOCATS trial aims to get underway this summer and will be offered as a chemotherapy alternative to individuals with advanced stage 4 ovarian cancers who are not suitable for immediate surgery and are not known to have a BRCA mutation.
“We are using our knowledge of what pathways in high-grade serous cancer are driving the tumours, and we’re trying to block them so that the tumour cannot continue to progress,” says Tone. “Tumours are smart, unfortunately. If you knock down only one pathway, a lot of tumours can just go around it. But if you actually target three pathways that are very important to this tumour’s survival, you don’t allow for those escape mechanisms, and you can shut down the very things that are driving the tumour.”