There currently 2 PARP inhibitors—olaparib and rucaparib—approved as monotherapies for the treatment of patients with metastatic castration-resistant prostate cancer.
Tian Zhang, MD, associate professor of Medicine at UT Southwestern Medical Center, discusses the potential of combination therapy with PARP inhibitors and novel androgen receptor targeted agents in patients with metastatic prostate cancer.
There currently 2 PARP inhibitors—olaparib (Lynparza) and rucaparib (Rubraca)—approved as monotherapies for the treatment of patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene mutations.
Monotherapies have accepted use across the board for patients with homologous recombination defects. And in particular, the TRITON3 data [for rucaparib] adds to our evidence in terms of supporting patients treated with PARP inhibitors versus either chemotherapy or an androgen receptor targeted agent. Now, when we're thinking across these populations, we are continuing to use PARP inhibitors as monotherapies. The biggest controversy in this space is whether we should be using them in combination with the androgen receptor targeted agents. Should we use the combination upfront for all patients with castration-resistant prostate cancer, regardless of homologous recombination status, or should we use them in a select patient population?
So that's one question. The second question is whether the combination of a PARP inhibitor with an AR targeted therapy is better than sequencing each as monotherapies. And so when we're thinking about these questions, oftentimes we're thinking through toxicity issues, affordability issues, and whether a patient is appropriate for the underlying androgen receptor targeted agent—all of these factor into whether or not they should be receiving the combination.
The transcript has been edited for clarity.