Men with metastatic castration-resistant prostate cancer (mCRPC) given Lynparza (olaparib), a breast and ovarian cancer treatment, went a clinically meaningful longer time without disease progression or death compared to those given standard treatment with Xtandi (enzalutamide) or Zytiga (abiraterone) in a Phase 3 trial.
The multicenter, open-label PROfound study (NCT02987543) compared the efficacy and safety of Lynparza to that of Xtandi (by Astellas and Pfizer Oncology) and Zytiga (by Janssen) in mCRPC patients whose disease had progressed while on these newer hormone treatments. Eligible patients also had a mutation in one of 15 genes involved in the homologous recombination (HR) pathway of DNA repair.
Specifically, these benefits were seen in patients with mutations in BRCA1, BRCA2, or ATM, the most common among HR gene mutations; the first two are also strongly linked with familial breast and ovarian cancers. Overall, HR mutations occur in approximately 25% of men diagnosed with mCRPC.
Lynparza, an oral PARP enzyme inhibitor marketed by AstraZeneca and Merck, is intended to prevent cancer cells from repairing DNA errors, causing their death. It is approved for some breast and ovarian cancers.
Patients in PROfound were treated with 300 mg twice daily of Lynparza, or investigators’ choice of Xtandi (160 mg daily) or Zytiga (1,000 mg daily, plus prednisone).
Lynparza’s safety and tolerability results were generally consistent with previous trials. AstraZeneca and Merck, known as MSD outside the U.S. and Canada, are planning to present full results at a future medical meeting. PROfound is expected to fully conclude in February 2021.
“This is the only positive Phase 3 trial of any PARP inhibitor in metastatic castration-resistant prostate cancer, where the need for new, effective therapies is high,” José Baselga, AstraZeneca’s executive vice president, Oncology R&D, said in a press release. “The PROfound trial also demonstrates the potential value of genomic testing in this at-risk patient population.
“We look forward to discussing these results with global health authorities soon,” he added.
Roy Baynes, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said trial results “represent the potential for a new, oral, and targeted treatment option for this patient population.”
Lynparza is being tested in other prostate cancer trials, including the international PROpel Phase 3 study testing the addition of Lynparza to Zytiga as a first-line treatment of mCRPC patients who have not been given chemotherapy or newer hormonal agents (NCT03732820). PROpel is currently enrolling up to 720 men at sites across the U.S., Canada, Europe and elsewhere. More information on locations and contacts is available here.