The use of PARP inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) has become an important area of research and clinical practice. However, there are still many questions about how to best sequence and treat patients with these agents. In a recent discussion among experts in the field, various approaches were considered for sequencing PARP inhibitors.
The first question posed was how to sequence PARP inhibitors for eligible patients with mCRPC. The general consensus was that PARP inhibitors should be used after the initial treatment, whether it is a new patient starting with doublet or triplet treatment, or after progression on another treatment. However, there was some variation in opinion about whether PARP inhibitors should be used earlier in patients with germline or somatic BRCA2 alterations. While some felt that these patients should receive PARP inhibitors early on in mCRPC, others felt that they should be used after progression on a prior agent.
The panel also discussed their approach to patients who progress on PARP inhibitors. One physician shared the case of a patient with a non-durable response to olaparib, despite having a deep response initially. The patient ultimately decided not to pursue further treatment due to comorbidities, but the physician noted that they were unsure what treatment to offer if the patient had chosen to continue. Another physician shared their experience treating a patient with an ATM mutation with PARP inhibitors, which did not result in a great response.
The panel also considered how to treat patients with non-BRCA pathogenic HRR mutations. One physician stated that they mostly use PARP inhibitors as a third-line treatment in patients with an ATM mutation, while another felt that they would consider using other treatments depending on what the patient had already received.
Finally, the panel discussed the design of recent trials looking at PARP inhibitors in mCRPC patients. One physician questioned the use of control arms in these trials, since sequential use of AR-targeted agents has been shown to be ineffective. However, another physician noted that these trials were designed before this evidence was available.
Overall, the discussion highlighted the need for further research and consensus-building around the sequencing and use of PARP inhibitors in mCRPC. There is still much to learn about which patients are most likely to benefit from these agents, how to best sequence them in the treatment paradigm, and what to do for patients who progress on them. However, the use of PARP inhibitors in mCRPC patients remains an area of active investigation and clinical interest.
