PARP inhibitor now approved for BRCA-mutated prostate cancer

GU cancer

By Mardi Chapman

6 May 2021

Olaparib (Lynparza) has been TGA approved for the treatment of patients with BRCA-mutated metastatic castration-resistant prostate cancer that has progressed following prior therapy including a new hormonal agent such as abiraterone and enzalutamide.

Evidence for the approval is largely based on the PROfound study, published in the NEJM last year, which found the PARP inhibitor was associated with a survival benefit in men with prostate cancer and BRCA1, BRCA2 or ATM alterations.

The study found PFS was 7.4 months in the olaparib group compared to 3.6 months in the control group who were on either enzalutamide or abiraterone (HR for progression or death 0.34; p<0.001).

Medical oncologist Dr Jeffrey Goh from Brisbane’s Greenslopes Private Hospital and Icon Cancer Centre, told the limbic that prostate cancer associated with BRCA1, BRCA2 and ATM mutations is a more aggressive disease.

“So now that there is a treatment that improves survival, BRCA/ATM mutation testing should be considered seriously although there is no funding for the testing as yet.”

“My belief is that men should be offered the test if they can afford it and if not, I hope that some mechanism of funding the test will be provided maybe through AstraZeneca compassionately or through the government funding it in the near future.”

He said women with high grade ovarian cancer had a 15-16% chance of carrying a BRCA mutation while men with prostate cancer had a much lower chance of about 4-5%.

“I think the cost to the government of funding olaparib is probably not going to be as much because only a small proportion of men will test positive for BRCA/ATM anyway, but that said, prostate cancer is a far more common cancer compared to ovarian cancer.”

He said clinical genetics /hereditary cancer clinics in some public hospitals were already picking up the tab for tests in patients with a very strong family history of ovarian and breast cancers.

“Men who carry the mutation are usually diagnosed at a relatively younger age and also there is possibly a family history of prostate cancer or a family history of breast and ovarian cancers.”

Other gene changes

Dr Goh noted the PROFound trial also included a second cohort of patients with alterations in any of 12 specified genes other than BRCA and ATM.

“And in that particular group, the benefit appears to be smaller with olaparib and is probably not significant. So at this stage we are still awaiting other trials to confirm the predictive ability of multi-gene panel or homologous recombination deficiency (HRD) testing in prostate cancer, as HRD testing has proven its utility in ovarian cancer. In prostate cancer to a lesser degree, ongoing trials are testing a panel of genes to correlate it with response to a PARP inhibitor.”

Other trials yet to report were using PARP inhibitors such as talazoparib and niraparib, trials combining PARP inhibitors with other drugs such as abiraterone or immunotherapy, and trials of treatment at an earlier stage of metastatic prostate cancer.

“It is a very exciting space and an exciting class of drugs.”

The TGA approval of olaparib for prostate cancer was welcomed by clinicians and advocates for men with prostate cancer.

Associate Professor Shahneen Sandhu of Peter MacCallum Cancer Centre, said olaparib represents the first personalised therapy for men with metastatic castration-resistant prostate cancer and an underlying BRCA1/2 alteration.

“I look forward to the day when molecular testing and personalisation of treatment becomes routine practice,” she said in a statement from AstraZeneca.

CEO of Prostate Cancer Foundation of Australia Professor Jeff Dunn said it was a significant step forward for hundreds of Australian men living with advanced prostate cancer.

“We are extremely pleased to see Australian authorities supporting the registration of new treatments for these men.”

Disclosures: Dr Goh is an advisor on ovarian and prostate cancer to a number of companies including AstraZeneca.

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