VIDEO: Upfront use of PARP, ARPI combination may offer greater survival benefit

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It makes sense that even though these drugs work by different mechanisms of action, that combinations are gonna be the most important ways of trying to eradicate the disease heterogeneity we know exists in prostate cancer, specifically, even though most prostate cancers are driven by androgen signaling, we know that if we have even very potent androgen deprivation therapy and androgen receptor pathway inhibitors, that we're not curing these patients with metastatic disease.

Because a subset of these patients actually have DNA damage repair mutations, we know that adding a PARP inhibitor in the setting of progression has been associated with improvements in survival, particularly with patients with BRCA one or two mutations. But the newer data really suggests that upfront use of the combination of an RP plus a PARP inhibitor may actually have a greater potential benefit, and in fact, a survival benefit. So certainly for patients who have a DNA damage repair mutation, such as BRCA two, they really should be getting the combination right up front of a PARP inhibitor and an RP.

And there are several to choose from. We'll have to see if we can improve on this by, for example, using it in the setting of MHSBC rather than waiting for castration resistance, or if there may be some combinations that might work even more broadly than just those with DNA damage repair mutations, it remains to be seen.