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.

Lu-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 

Lu-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.

Videos

Alicia Morgans, MD, MPH, discusses current androgen deprivation therapy combinations and the investigation of radiopharmaceutical combinations for metastatic hormone-sensitive prostate cancer. 

Dr. Morgans on the Current Treatment Landscape For mHSPC

Alicia Morgan, MD, Mather Hospital, discusses combinations with PARP inhibitors in prostate cancer.

With the advent of PARP inhibitors in prostate cancer, Morgan says that investigators are considering these agents in combination with already-established treatment modalities. PARP inhibitors are being looked at with androgen receptor-directed therapies, immunotherapy approaches, and radiation.

Additionally, there is interest in understanding whether there is a synergistic action with platinum agents. There is some evidence that patients who have DNA repair defects may be more sensitive to agents such as carboplatin compared to traditional chemotherapy with docetaxel.

Morgan says that the potential of adding other therapies to PARP inhibitors is exciting, and combinations will hopefully be a part of the future treatment landscape of prostate cancer.

Alicia Morgan, MD, Mather Hospital, discusses combinations with PARP inhibitors in prostate cancer.
 

Dr. Morgan on Combinations With PARP Inhibitors in Prostate Cancer

Alicia Morgan, MD, Mather Hospital, discusses the impact of PARP inhibitors in prostate cancer.

Initially, the prostate cancer community did not realize how big of a potential role there was for PARP inhibitors in the treatment landscape, says Morgan. There are many reasons that the prostate cancer community is excited about the option of PARP inhibitors, one being the benefit that PARP inhibitors have shown in other solid tumor types.

Other than that, the oral aspect of PARP inhibitors is appealing, says Morgan, as patients do not have to come into the clinic to receive infusions and the regimen is tolerable. Morgan adds that the idea of a targeted treatment other than androgen receptor-directed therapy in the treatment of patients with prostate cancer is exciting.

In January 2016, the FDA granted the PARP inhibitor olaparib (Lynparza) a breakthrough therapy designation as a treatment for patients with 

-mutated metastatic castration-resistant prostate cancer who have received prior taxane-based chemotherapy and at least either enzalutamide (Xtandi) or abiraterone acetate (Zytiga).

Dr. Morgan Discusses the Impact of PARP Inhibitors in Prostate Cancer

Alicia Morgan, MD, Mather Hospital, discusses enrolling patients with prostate cancer onto clinical trials investigating PARP inhibitors.

According to Morgan, medical oncologists and urologists need to think strongly about getting genomic and genetic sequencing data for their patients as they are approaching a time when they might use PARP inhibitors. For most community oncologists, this is going to be after they have used FDA-approved agents, such as enzalutamide (Xtandi), abiraterone acetate (Zytiga), and chemotherapy, as well as our other therapies, such as immunotherapies and pharmaceutical options.

If the physician can receive the genomic and genetic sequencing data, they might be able to get off-label PARP inhibitors, says Morgan. It is important to advise patients to go to a clinical trial at an academic center to get more data with PARP inhibitors.

One of the challenges that is seen for men with prostate cancer is there are so many trials available with PARP inhibitors that there is a concern that there may be too many trials and not enough patients. Morgan encourages urologists and medical oncologists with any interest in this to identify their patients. For those patients who are able to enroll, the oncologists could try to get them to clinical trials to help build the data to move this field forward.

Dr. Morgan on Enrolling Patients With Prostate Cancer onto Clinical Trials

Alicia Morgan, MD, Mather Hospital, discusses the role of PARP inhibitors for patients with prostate cancer.

According to Morgan, PARP inhibitors are a fascinating targeted therapy in prostate cancer. Both medical oncologists and urologists need to consider who should receive these drugs. They do have some toxicities—they can make patients tired, and have other effects on bone marrow suppression.

Any treatment that is used, especially a targeted treatment, says Morgan, should attempt to target the right population to understand that population more clearly and thoroughly. Using these agents in those who will respond can go a long way toward improving outcomes in patients with prostate cancer.

Currently, there is an ongoing phase III trial (NCT02987543) investigating the PARP inhibitor olaparib (Lynparza) versus enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in patients who have failed prior treatment with a new hormonal agent and have homologous recombination repair gene mutations.

Approximately 340 patients will be randomized 2:1 to either the olaparib arm or the enzalutamide/abiraterone arm, respectively. The primary results of this study are expected to be seen in 2020.

Dr. Morgan on the Role of PARP Inhibitors in Prostate Cancer

Alicia Morgan, MD, Mather Hospital, discusses the role of olaparib (Lynparza) for patients with metastatic castration-resistant prostate cancer (mCRPC).

Olaparib is a PARP inhibitor for the treatment of patients with mCRPC. In the TOPARP-A study, men were selected if they had undergone multiple prior therapies and were treatment refractory, explains Morgan. The response rate of patients who had DNA repair defects was 88%, based on prostate-specific antigen (PSA) response.

According to Morgan, the response was higher than what is traditionally expected in a regular clinical trial.

Alicia Morgan, MD, Mather Hospital, discusses the role of olaparib (Lynparza) for patients with metastatic castration-resistant prostate cancer (mCRPC).
 

Alicia Morgan, MD

Articles

Dr. Morgans on the Current Treatment Landscape For mHSPC

Dr. Morgan on Combinations With PARP Inhibitors in Prostate Cancer

Dr. Morgan Discusses the Impact of PARP Inhibitors in Prostate Cancer

Dr. Morgan on Enrolling Patients With Prostate Cancer onto Clinical Trials

Dr. Morgan on the Role of PARP Inhibitors in Prostate Cancer

Dr. Morgan on Olaparib for Metastatic Castration-Resistant Prostate Cancer