Alicia Morgan, MD

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.

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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.

Author | Alicia Morgan, MD

Articles

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