Tanya B. Dorff, MD, associate clinical professor in the Department of Medical Oncology and Therapeutics Research, and head of the genitourinary cancers program at City of Hope, discusses the use of PARP inhibitors in prostate cancer.

 showed the efficacy of PARP inhibitors in prostate cancer. Specifically, the authors reported that olaparib (Lynparza) led to responses in a high percentage of patients with prostate cancer who had DNA repair defects. There are several PARP inhibitors being studied in ongoing clinical trials, and early data suggest this strategy will have a more prominent role in the future, says Dorff. The key will be identifying the right mutations to target as well as defining the optimal settings for use, she adds.

Olaparib has already been tested in a phase III study against physician’s choice of docetaxel, abiraterone acetate (Zytiga), or enzalutamide (Xtandi). Within the next couple of years, comparative data should allow researchers to effectively place PARP inhibitors in the prostate cancer landscape.

Videos

Dr. Dorff Discusses the Use of PARP Inhibitors in Prostate Cancer

PARP inhibitors will likely be the next drugs approved for patients with prostate cancer, says Dorff. Several phase III trials have completed, with results showing that these drugs are effective in patients with 

-mutated disease as well as certain other DNA-repair deficiency populations.

Moving forward, physicians are going to see comparative studies of olaparib (Lynparza) versus physician's choice of abiraterone acetate (Zytiga), enzalutamide (Xtandi), or docetaxel. Those studies are going to be important in terms of benchmarking, as they will serve as the first sets of directly comparative data on existing versus emerging strategies. Having these data available will have a huge impact, adds Dorff. Only 20% or 25% of patients have these mutations, but for those who do, it's going to be a very beneficial tool to have, she concludes.

Dr. Dorff on PARP Inhibitors in Prostate Cancer

Tanya B. Dorff, MD, associate clinical professor in the Department of Medical Oncology and Therapeutics Research, and head of the genitourinary cancers program at City of Hope, discusses sequencing in metastatic castration-resistant prostate cancer (mCRPC).

Treating physicians have more options now than ever before for the treatment of patients with mCRPC, explains Dorff. Modern therapies have been shown to prolong survival, maintain a good quality of life, and reduce skeletal symptomatic events, says Dorff. However, there is no one right sequence, and in the absence of comparative data between these agents, physicians should individualize each treatment to each patient, she says.

A physician may be inclined to give a patient chemotherapy after they have received either abiraterone (Zytiga) or enzalutamide (Xtandi); however, the patient may be unable to quit their job to receive therapy or he/she may have other comorbidities that may prevent them from receiving the chemotherapy. Radium-223 dichloride (Xofigo) is a suitable option for patients with bone-only or metastatic disease that is limited to the bone, says Dorff, whereas this would not be the appropriate choice for patients with soft tissue and visceral metastases. Moreover, there is immunotherapy with sipuleucel-T (Provenge) for select patients who are minimally symptomatic or asymptomatic, and have slowly progressing disease, she adds.

In addition to considering clinical features to help determine the optimal therapy for patients, imagining can sometimes alert physicians to a potential need to switch or sustain therapy.

Dr. Dorff on Sequencing in Metastatic Castration-Resistant Prostate Cancer

Tanya B. Dorff, MD, associate clinical professor in the Department of Medical Oncology and Therapeutics Research, and head of the genitourinary cancers program at City of Hope, discusses the status of immunotherapy in prostate cancer.

In addition to research focused on patients in the metastatic hormone-sensitive setting as well as those in biochemical recurrence, efforts are being made with a specific focus on providing patients with more durable remissions without sacrificing quality of life. As this is a longer-term disease process, says Dorff, many of the newer studies are recording patient-reported outcomes, which is very important.

Immunotherapy is another area of opportunity although immune checkpoint inhibitors have not shown as substantial of a benefit in these patients as physicians would like. Sipuleucel-T (Provenge) is a form of immunotherapy that has demonstrated benefit, although modest in men with prostate cancer. Physicians are hoping that more research will lead to a game-changing immunotherapy for this patient population.

Studies are underway in which investigators are evaluating combinations of radiation with immunotherapy, immunotherapy with immunotherapy, as well as exploring which hormone therapies are the most immunogenic. Although it may take some time before these approaches are incorporated into clinical practice, Dorff anticipates that options will be available within the next 5 years.

Dr. Dorff on the Status of Immunotherapy in Prostate Cancer

Tanya B. Dorff, MD, associate clinical professor, Department of Medical Oncology and Therapeutics Research, head, Genitourinary Cancers Program, City of Hope, discusses choosing between therapies in nonmetastatic castration-resistant prostate cancer (CRPC).

Last year brought 2 new agents into this treatment paradigm, said Dorff: apalutamide (Erleada) and enzalutamide (Xtandi). These drugs have not yet been compared head-to-head, so although they are both acceptable options, it is currently up to the physician and patient to decide which option is the right one for each case. Although there are slight differences in their side effect profile, says Dorff, there is no substantial reason for choosing one over the other.

These agents are effective in prolonging survival, but another important endpoint is maintaining quality of life, she adds. Bone fractures are a common adverse event associated with these treatment options, so additional bone therapy is something that needs to be strongly considered.

In February 2018, apalutamide became the first drug to be approved by the FDA for use in patients with nonmetastatic CRPC, following the positive results from the phase III SPARTAN trial. This study showed a 72% decrease in the risk of metastases or death with apalutamide versus placebo. Based on the phase III PROSPER study, enzalutamide followed suit in July 2018, when the data showed a metastasis-free survival of 36.6 months with the agent when used in combination with androgen deprivation therapy.

Tanya B. Dorff, MD, associate clinical professor, Department of Medical Oncology and Therapeutics Research, head, Genitourinary Cancers Program, City of Hope, discusses choosing between therapies in nonmetastatic castration-resistant prostate cancer.

Dr. Dorff on Choosing Between Therapies in Nonmetastatic CRPC

Tanya B. Dorff, MD, associate professor of clinical medicine, University of Southern California, discusses current agents available for patients with metastatic castration-resistant prostate cancer (mCRPC).

There are several agents available to treat patients with mCRPC, such as abiraterone acetate (Zytiga), enzalutamide (Xtandi), and docetaxel. However, patients treated with upfront intensification complicates the treatment process, says Dorff.

Novel agents, such as immunotherapy and PARP inhibitors, are being compared to these older agents in clinical trials, explains Dorff.

Tanya B. Dorff, MD

Articles

Dr. Dorff Discusses the Use of PARP Inhibitors in Prostate Cancer

Dr. Dorff on PARP Inhibitors in Prostate Cancer

Dr. Dorff on Sequencing in Metastatic Castration-Resistant Prostate Cancer

Dr. Dorff on the Status of Immunotherapy in Prostate Cancer

Dr. Dorff on Choosing Between Therapies in Nonmetastatic CRPC

Dr. Dorff on Current Agents for Patients With mCRPC