AstraZeneca and Merck & Co. announced Friday that Lynparza (olaparib) demonstrated a significant and clinically meaningful improvement in overall survival (OS) versus new hormonal agent treatments in men with metastatic castration-resistant prostate cancer (mCRPC) selected for BRCA1/2 or ATM gene mutations, a subpopulation of homologous recombination repair (HRR) gene mutations. The companies reported in August that the Phase III PROfound trial met its primary endpoint of significantly improving radiographic progression-free survival (rPFS).
José Baselga, executive vice president of oncology R&D at AstraZeneca, said "overall survival in metastatic castration-resistant prostate cancer has remained extremely challenging to achieve. We are thrilled by these results for Lynparza and we are working with regulatory authorities to bring this medicine to patients as soon as possible."
The study is evaluating the efficacy of Lynparza versus Astellas and Pfizer's Xtandi (enzalutamide) or Johnson & Johnson's Zytiga (abiraterone) in patients with mCRPC who have progressed on prior treatment with new hormonal agent treatments and have a qualifying tumour mutation in BRCA1/2, ATM or one of 12 other genes involved in the HRR pathway. The trial's primary endpoint was rPFS in patients with mutations in BRCA1/2 or ATM genes, while key secondary goals included rPFS in the overall trial population of patients with HRR gene mutations and OS in patients selected for BRCA1/2 or ATM gene mutations.
Results disclosed at last year's European Society for Medical Oncology (ESMO) congress showed that for the primary endpoint, Lynparza reduced the risk of disease progression or death by up to 66%, while in the overall population of patients with HRR gene mutations, the PARP inhibitor cut the risk of disease progression or death by 51%.
Roy Baynes, head of global clinical development at Merck Research Laboratories, said "Lynparza has demonstrated significant clinical benefit across key endpoints in PROfound, including overall survival for patients with BRCA or ATM mutations, and this reinforces its potential to change the treatment standard for patients with metastatic castration-resistant prostate cancer." The companies noted that the latest data will be presented at a future medical meeting.
In January, the FDA granted priority review to a marketing application seeking approval of Lynparza for patients with mCRPC and deleterious or suspected deleterious germline or somatic HRR gene mutations, who have progressed following prior treatment with a new hormonal agent. The agency is scheduled to make a decision on the filing in the second quarter, while regulatory reviews are ongoing in the EU and other countries.
AstraZeneca and Merck are also investigating Lynparza in the Phase III PROpel trial as a first-line treatment for patients with mCRPC in combination with Zytiga versus Zytiga alone, with the first data expected in 2021. Earlier this year, the UK drugmaker reported that sales of Lynparza in the fourth quarter of 2019 jumped 68% to $351 million.
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