ESMO19: AstraZeneca, Merck & Co.'s PARP inhibitor Lynparza cuts risk of disease progression, death in prostate cancer trial

AstraZeneca and Merck & Co. said Monday that in the Phase III PROfound trial, the PARP inhibitor Lynparza (olaparib) reduced the risk of disease progression or death by up to 66% in men with metastatic castration-resistant prostate cancer (mCRPC) who have a mutation in their homologous recombination repair (HRRm) genes and whose disease had progressed on prior treatment with new hormonal agent treatments. Findings from the study, which the companies reported in August met its main goal, were detailed at the European Society for Medical Oncology (ESMO) congress.

Results presented at ESMO showed a significant and clinically meaningful improvement with Lynparza in the primary endpoint of radiographic progression-free survival (rPFS), improving the time men with BRCA1/2- or ATM-mutated mCRPC lived without disease progression or death to a median of 7.4 months, compared to 3.6 months for those treated with new hormonal agent treatments. AstraZeneca and Merck added that the trial also met the key secondary goal of rPFS in the overall HRRm population, where Lynparza cut the risk of disease progression or death by 51% and improved rPFS to a median of 5.8 months from 3.5 months in patients who received treatment with a new hormonal agent.

"To see such a significant effect on disease progression and other clinically relevant effects such as pain progression and objective response rate is a remarkable achievement in such heavily pre-treated patients with prostate cancer," remarked study author Maha Hussain. The researcher said "prostate cancer has lagged behind all other common solid tumours in the use of molecularly targeted treatment so it is very exciting that now we can personalise an individual’s treatment based on specific genomic alterations in their cancer cells."

According to the drugmakers, although adverse events were more common in the Lynparza group, the median treatment duration was 7.4 months for Lynparza, nearly double the treatment duration of 3.9 months for hormonal treatment. Meanwhile, the treatment discontinuation rates due to adverse events were 16.4% for Lynparza and 8.5% for hormonal therapy.

Commenting on the news, Nicholas James of Cancer Research UK remarked "matching patients to the most appropriate treatment for their tumour type could radically change the way we treat prostate cancer," continuing "if we get to a point where we can tailor treatments in prostate cancer from an early stage, we can give every patient the best chance of being successfully treated." 

AstraZeneca and Merck are jointly developing and marketing Lynparza under the terms of a 2017 partnership. Sales of the treatment reached $283 million in the second quarter. 



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