Alicia Morgans, MD, on Going Beyond ADT for Metastatic Prostate Cancer

Androgen-deprivation therapy (ADT) is no longer the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC), outside of select populations with limited life expectancy, contraindications, or personal preferences, said the authors of an Oncology Grand Rounds paper in the Journal of Oncology.

Instead, more-intense therapy is preferred -- either a combination of ADT with docetaxel or an androgen receptor signaling inhibitor, or triplet therapy with all three in fit patients with high-volume disease who prefer to intensify treatment, said Alicia Morgans, MD, and Himisha Beltran, MD, both of Dana-Farber Cancer Institute in Boston.

"Only by approaching each patient from the perspective of guiding them to the best combination option first and a reflexing to ADT monotherapy as an option when no intensification strategy is possible, can we ensure that all patients have access to treatment that is expected to provide the best disease control and quality of life in this setting," Morgans and Beltran wrote.

In the following interview, Morgans, who is medical director of Dana-Farber's Survivorship Program, elaborated on the information in the paper.

Why is androgen-deprivation therapy no longer the standard of care, outside of certain populations?

Morgans: Since the initial CHAARTED trial was reported in 2014, we have had multiple phase III studies that clearly demonstrate superior disease control and improved quality of life for combination treatments versus ADT alone in patients with mHSPC.

There were no patient populations in which ADT alone was better than combination treatment. Especially when we consider the oral androgen receptor signaling inhibitors like abiraterone acetate, apalutamide, and enzalutamide in combination with ADT, there are very few patient- or disease-related reasons to avoid combination treatments.

Unfortunately, we see in real-world populations that despite numerous trials providing level one evidence that combination treatment is superior in terms of all disease control and quality-of-life outcomes, approximately 50% of men in the U.S. are getting substandard treatment with ADT alone.

We must do better for our patients and give them the combination treatments that have clearly demonstrated superiority in cancer control and quality-of-life outcomes unless there is an extremely compelling reason not to do this.

In discussing factors that go into treatment decisions, you covered cancer-related, treatment-related, and patient-related factors. But you also included clinician-related factors? What are the clinician-related factors?

Morgans: Clinician-related factors that can affect treatment decisions include things like physician familiarity and comfort with prescribing specific drugs, access to infusion facilities to deliver treatment, and staff ability to support patients with complications and adverse events.

You mentioned the importance of shared decision-making. Do you have any advice about how to discuss treatment options with patients to help make the choice that is best for them?

Morgans: Shared decision-making is so important in oncology, especially in settings in which there are multiple options for treatment that are similar in terms of cancer control but different in terms of things that matter to patients, like cost, dosing method and schedule, infection risk, and quality-of-life effects.

When facing decisions for men with mHSPC, I have had the most success by starting ADT first and sharing information about combination treatment options when that occurs, but allowing patients to think and ask questions over the next few weeks about which treatment combination will be best for him.

In the clinical trials that demonstrated the benefit of combination treatment, patients typically started intensified therapy within 12-16 weeks of starting ADT. Mimicking this approach gives patients time to consider their options, talk with their family, and really choose the treatment that is best for them.

What role do molecular biomarkers play in informing treatment decisions, and what role may they play in the future?

Morgans: At present we use imaging as a biomarker to define whether patients have high- or low-volume metastatic disease. This is very important for treatment decision-making in mHSPC. However, we anticipate that in the future we will be able to use molecular testing to provide a risk score or signature that will suggest whether combining ADT with chemotherapy or an androgen receptor signaling inhibitor might be more or less helpful, and maybe even whether triplet therapy is preferred over doublet treatment.

Read the Grand Rounds paper here.