A combination of the investigational therapy cediranib and Lynparza (olaparib) fails to delay disease progression in women with platinum-sensitive relapsed ovarian cancer compared with standard platinum-based chemotherapy, findings from a Phase 3 trial show.
The results mean that the trial’s main goal — progression-free survival — was not met. Researchers at NRG Oncology, who are leading the trial in collaboration with the National Cancer Institute (NCI), are now examining the full data to inform the future of the clinical trial and their ongoing research.
“Despite these disappointing results, we remain committed to expanding on the benefits already demonstrated with Lynparza for patients with advanced ovarian cancer,” José Baselga, MD, PhD, executive vice president of oncology research and development at AstraZeneca, said in a press release. “We will work closely with NRG Oncology and the NCI to review the full results to inform our ongoing research.”
Lynpaza, an oral PARP inhibitor that’s been approved for three ovarian cancer indications, acts by blocking the activity of the PARP enzyme, which works as a sensor of DNA damage. By blocking PARP activity, Lynparza leads to the accumulation of DNA damage, which ultimately results in the death of cancer cells.
Combining multiple treatments is often a more effective cancer treatment than using single treatments alone, which led a team at NRG Oncology to collaborate with AstraZeneca to study a combination of Lynpaza and cediranib.
Cediranib, developed by AstraZeneca, is an orally administered inhibitor of the protein vascular endothelial growth factor receptor (VEGFR), a key factor for the formation of new blood vessels that support tumor growth. It works in a similar manner as bevacizumab, a mainstay treatment for ovarian cancer patients.
Use of cediranib is associated with anti-tumour activity across several cancers, including ovarian, breast, colorectal, renal, lung, sarcoma, and glioblastoma.
The ongoing GY004 Phase 3 trial (NCT02446600) was designed to include about 550 ovarian cancer patients who had responded to prior platinum-based chemotherapy, but whose cancer eventually relapsed.
The goal was to determine if a combination of Lynparza plus cediranib was better than standard platinum-based chemotherapy at extending the time patients lived without having signs of disease progression. Secondary measures included overall survival, safety, and patient-reported symptoms.
The trial did not meet it primary endpoint, meaning that the Lynparza combination is no better than standard chemo at delaying disease progression or death. Additional results indicate that the safety and tolerability profiles of both cediranib and Lynparza were consistent with those known for each medicine alone.
“Ovarian cancer is one of the most difficult tumors to diagnose and treat early,” said Roy Baynes, MD, PhD, senior vice president and chief medical officer at MSD Research Laboratories. “AstraZeneca, MSD and our partners will continue to explore ways to help patients through our joint clinical trial development program.”
Three additional trials are now continuing to explore combinations of Lynparza and cediranib in ovarian cancer patients: the CONCERTO Phase 2 trial (NCT02889900) for women with platinum-resistant ovarian cancer, the ICON9 Phase 3 trial (NCT03278717) for the maintenance treatment of patients with relapsed ovarian cancer who are responding to platinum-based chemotherapy, and the GY005 Phase 2/3 trial (NCT02502266) for women whose cancer failed to respond or returned after responding to platinum-based chemotherapy.