Future Directions in Metastatic PC: Exploring Monotherapy, Novel Therapies, and Strategic Sequencing

A roundtable discussion, moderated by Jigarkumar Parikh, MD, MBBS, highlighted the evolving landscape of prostate cancer treatment through the integration of multi-specialty collaboration, the introduction of new therapies and their challenges, and the crucial role of molecular and genetic testing in personalizing patient care and improving long-term outcomes. Dr. Parikh was joined by Joshua Perkel, MD; Rajesh Laungani, MD; Joseph Bear, MD; and Marc Greenstein, DO.

In the fifth segment of the roundtable series, the panel ponders the future of metastatic prostate cancer treatment, emphasizing the potential of emerging therapies, such as monotherapy and targeted agents, and the importance of sequencing treatments and addressing patient concerns related to PSA levels and quality of life.

View the next segment of the roundtable series: Evolving Metastatic PC Care: Integrating New Therapies, PSA Management, and Molecular Analysis.

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Dr. Parikh: How do we see this evolving field going forward? We have excellent data, and sequencing of these drugs is also important, especially in the medical oncology field. We want to use the best available therapy upfront, which is the triplet therapy. How do you think about what comes next? After triplet therapy, if patients progress, what are the options? How do you approach this?

Dr. Perkel: One of the frontiers is that patients often ask if they still need to receive injections after starting a novel oral medication with ADT. Some trials are ongoing with monotherapy orals that look promising. It will be interesting to see if cardiovascular risks associated with medications like leuprolide can be minimized with oral agents alone. This could potentially improve quality of life and reduce long-term toxicities if patients could switch to an oral agent for maintenance after initial treatment.

Dr. Laungani: The natural progression has been that treatments initially approved for castrate-resistant prostate cancer eventually extend to hormone-sensitive prostate cancer. Typically, once a drug is approved, others in the same class follow suit. The next logical step would be to explore monotherapy options and see if eliminating the significant side effects of Lupron or Orgovyx can lead to major improvements, particularly in terms of cardiovascular risk. Monotherapy could significantly enhance quality of life and treatment efficacy for prostate cancer.

Dr. Parikh: Yes, cardiovascular health is a major concern, especially since patients may be on hormone treatment for many years. Close monitoring of heart health is essential. This underscores the importance of collaborating with specialists, including cardiologists, particularly if patients have a known cardiac history.

What about other newer therapies? Lutetium-177 has been approved for metastatic castrate-resistant prostate cancer, and there are ongoing studies to move these agents into a frontline setting. We anticipate a lot of new data and potentially new sequencing regimens in the future. How do you view the current and future landscape with these new data?

Dr. Greenstein: My first experience with lutetium involved patients traveling to Germany for treatment. They would return home, and after a year or so, they would need to go back for another round. Now that it is available locally, it is a significant advancement. It would not surprise me if, in the near future, lutetium might be approved before chemotherapy.

Dr. Parikh: So, it might be approved for use prior to chemotherapy. Understood.

Dr. Greenstein: Yes, because it targets specific cells, unlike chemotherapy, which is more systemic.

Dr. Parikh: This also highlights the importance of drug availability. Prostate cancer is prevalent, and when new drugs are approved, we need to ensure they are available in sufficient quantities. Early availability is crucial, and we hope the industry will be prepared to meet patient needs promptly.

Dr. Laungani: May I ask a question? What is your algorithm for using novel therapies or receptor inhibitors? How do you decide which one to use first? Do you save one for later, or is one preferred over the others? Is it based on side effect profiles or other factors? This process often seems like a matter of chance, such as choosing ADT plus one agent or another.

Dr. Parikh: This situation is more common in the castrate-resistant population. They are already on ADT and likely have undergone chemotherapy, which is increasingly used upfront in hormone-sensitive cases. Among the currently approved oral androgen receptor inhibitors for castrate-resistant cases, Zytiga and Xtandi both have similar efficacy. The choice may depend on factors like the need for prednisone with Zytiga or concerns about neurological side effects. Xtandi might be preferred if there is a risk of seizures or CNS issues.

Many practices have their own preferences for using one agent over another to simplify the process. This can be helpful given the many stakeholders involved, including pharmacists, patient assistance teams, and nurse navigators.

Dr. Perkel: There is also a consideration for darolutamide, which is approved for non-metastatic castrate-resistant prostate cancer but can be used for lymph node-positive cases up to 2 centimeters in size. This offers an additional treatment option for patients who tolerate it well.

Dr. Parikh: Yes, that is an excellent point. The ARAMIS trial examined darolutamide in non-metastatic castration-resistant prostate cancer patients, including those with lymph node involvement up to 2 centimeters. For such patients, darolutamide combined with ADT would be an excellent choice. Good point.