MSD and AstraZeneca have announced that in the PROfound trial, Lynparza (olaparib) more than doubled median radiographic progression-free survival in certain types of metastatic prostate cancer.
The drug gained the positive results in the trial of 387 men with metastatic castration-resistant prostate cancer (mCRPC) who have a mutation in their homologous recombination repair (HRR) genes and whose disease had progressed on prior treatment with new hormonal agent (NHA) treatments e.g. abiraterone or enzalutamide.
Designed to analyse men with mCRPC harboring HRR-mutated (HRRm) genes in two cohorts, the trial’s primary endpoint was in those with mutations in BRCA1/2 or ATM genes and then, if the treatment showed clinical benefit, a formal analysis was performed of the overall trial population of men with HRRm genes.
The companies announced that the results showed a statistically-significant and clinically-meaningful improvement in the primary endpoint of radiographic progression-free survival, thus reducing the risk of disease progression or death by a median of 7.4 months versus 3.6 months.
The results, presented at the 2019 European Society of Medical Oncology (ESMO) congress, show that the drug also met the key secondary endpoint of the trial, reducing the risk of disease progression or death by 51% and improving rPFS to a median of 5.8 months vs. 3.5 months.
Dr José Baselga, executive vice president, oncology R&D, AstraZeneca, said that the results demonstrate that “in addition to providing substantial benefit as a precision medicine for men with metastatic castration-resistant prostate cancer with BRCA-mutated tumours, Lynparza is effective beyond just BRCA in tumours with mutations in other genes associated with homologous recombination repair.”
He continued, “PROfound validates the concept of PARP sensitivity across multiple genes associated with homologous recombination repair in this disease and marks the first positive Phase III trial using a molecular biomarker to identify men for targeted treatment for metastatic castration-resistant prostate cancer. We are working with global health authorities to bring Lynparza to these patients as quickly as possible.”
Prostate cancer is the second most common cancer in men, with an estimated 1.6 million new cases diagnosed worldwide in 2015 and is associated with a significant mortality rate.