TRITON2: Rucaparib for metastatic castration-resistant prostate cancer

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Published: 7 Oct 2019
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Prof Ray McDermott - St. Vincents University Hospital, Dublin, Republic of Ireland

Prof Ray McDermott speaks to ecancer at ESMO 2019 in Barcelona about the TRITON2 study.

This is for patients with DNA damage repair (DDR)-deficient metastatic castration-resistant prostate cancer, and they were treated with rucaparib.

Prof McDermott outlines the positive results, and explains how testing for these DDR mutations is important, as the implications for this subset of patients is good.

The TRITON2 study is for patients with metastatic castrate resistant prostate cancer who have had prior novel antiandrogen and one line of prior chemotherapy. It’s a single arm study for patients who have one of a number of DDR deficiencies which would suggest that a PARP inhibitor might be effective in that population. Predominantly BRCA1 and 2 but also at the beginning of the study ATM, CHEK and a cohort of other genes in that family.

The results that were published today, the poster was today, has shown very promising activity, particularly in the BRCA1 and 2 population, with, in patients with measurable disease, a response rate around the 50% mark. In the PSA response it’s slightly higher than that. The responses would appear to be durable and the drug is well tolerated. So overall good news for these patients.

What could be the implications going forward?

Firstly it means that we need to be testing patients for these defects. You can do that in two ways, you can have a germline mutation or you can develop one as your cancer progresses. So you need to be testing patients later on in their disease process as well as doing the germline testing. That obviously has challenges for us as physicians and also for our administrators and how to pay for that. Because we need to identify these patients because the clinical benefit, this is an oral agent which is relatively well tolerated, so the implications for the patients are good. If they have one of these mutations they’re going to have another treatment which will add time without their disease progressing and hopefully give them a better quality of life. Therefore they should get it; if they’re suitable for it they should get one of these drugs.

There are some side effects, particularly nausea at the beginning, fatigue is another issue that can arise and anaemia. They’re probably the biggest side effects that we’ve seen with the drug. But, generally speaking, the number of people that have to come off the drug because of adverse events is low and it’s usually manageable, the toxicity is very manageable for most patients.

What’s next for the study?

This is in patients who have had chemotherapy and a novel antiandrogen, there’s also a randomised study which is TRITON3 which is earlier on in the disease process – randomisation to the physician’s treatment of choice, whether it be chemotherapy or another antiandrogen. I think you’ll see today but also tomorrow that PARP inhibitors are going to come earlier in the disease process in prostate cancer, a bit like we’ve seen in other diseases.