Dr. Morgans on the Current Treatment Landscape For mHSPC

Alicia Morgans, MD, MPH, member, faculty of medicine, Harvard Medical School, medical director, Survivorship Program, Dana-Farber Cancer Institute, discusses the current landscape of androgen deprivation therapy (ADT) combinations and the investigation of radiopharmaceutical combinations for metastatic hormone-sensitive prostate cancer (mHSPC). 

The standard treatment for mHSPC involves androgen receptor pathway inhibitors (ARPI) in combination with ADT, Morgans begins. These regimens include abiraterone acetate (Zytiga) and prednisone, enzalutamide (Xtandi), and apalutamide (Erleada). Triplet therapies are another viable option and are particularly effective for patients with de novo metastatic and high-volume metastatic disease, she says. These include administration of ADT, 6 cycles of docetaxel, and either darolutimide (Nubeqa) or abiraterone until the time of disease progression. When combined with ADT, these regimens can improve overall survival and maintain quality of life in this patient population, Morgans states.

Radiopharmaceutical combinations are another area of great interest for the treatment in mHSPC, Morgans continues. One of the most highly anticipated trials in the mHSPC setting is the phase 3 PSMAddition trial (NCT04720157), she says. The prospective, randomized trial will evaluate the efficacy and safety of adding high-affinity prostate-specific membrane antigen (PSMA)-targeted radioligand therapy Lutetium 177 (177Lu) PSMA-617 (177Lu-PSMA-617; Pluvicto) to SOC ADT plus an ARPI. The triplet combination will be compared with ADT plus an ARPI in adult patients with PSMA-positive mHSPC who are either treatment-naïve or minimally treated with hormonal therapy.

¹⁷⁷Lu-PSMA-617 was approved by the FDA for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in March 2022, Morgans notes. Previous results from the pivotal phase 3 VISION trial (NCT03511664) demonstrated that ¹⁷⁷Lu-PSMA-617 improved median overall survival and was well tolerated vs best supportive care in patients with PSMA-positive mCRPC. Data also indicate that its use in combination with an ARPI will remain tolerable. Therefore, efforts to utilize this therapy in mHSPC are both exciting and promising, Morgans concludes.