Manish Kohli, MD, vice chair, Department of Genitourinary Oncology, Moffitt Cancer Center, discusses the use of enzalutamide (Xtandi) and apalutamide (Erleada) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

In the phase 3 ENZAMET study, investigators evaluated the combination of enzalutamide with docetaxel in men with mHSPC. The seizure rates, in addition to the neuropathy and fatigue rates, were higher with the combination. As the data mature, it will be important to assess the risk-benefit ratio of adding another agent to the mix, says Kohli.

Apalutamide is another option based on the results from the phase 3 TITAN trial. The interim results from the trial are comparable with abiraterone acetate (Zytiga) and docetaxel, says Kohli. Though, there were some extra adverse effects (AEs), such as pruritus and rash, which were not seen with the other drugs. However, each agent has a different set of AEs. The decision of which agent to pursue largely depends on tolerability, concludes Kohli.

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Manish Kohli, MD, discusses the use of enzalutamide (Xtandi) and apalutamide (Erleada) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Dr. Kohli on the Use of Enzalutamide and Apalutamide in mHSPC

In the phase 3 ENZAMET study, investigators evaluated the combination of enzalutamide with docetaxel in men with mHSPC. The seizure rates, in addition to the neuropathy and fatigue rates, were higher with the combination. As the data mature, it will be important to assess the risk-benefit ratio of adding another agent to the mix, says Kohli.

Apalutamide is another option based on the results from the phase 3 TITAN trial. The interim results from the trial are comparable with abiraterone acetate (Zytiga) and docetaxel, says Kohli. Though, there were some extra adverse effects (AEs), such as pruritus and rash, which were not seen with the other drugs. However, each agent has a different set of AEs. The decision of which agent to pursue largely depends on tolerability, concludes Kohli.

Manish Kohli, MD, vice chair, Department of Genitourinary Oncology, Moffitt Cancer Center, discusses drugs that have been evaluated in metastatic castration-resistant prostate cancer (mCRPC).

Several single agents have been shown to have an overall survival benefit in patients with mCRPC; however, combination approaches have yet to show the same benefit, says Kohli. 

For example, radium-223 dichloride (Xofigo) was combined with abiraterone acetate (Zytiga) and prednisone in the phase III ERA 223 trial. However, the combination failed to demonstrate a delay in skeletal-related complications versus abiraterone acetate/prednisone and placebo. As such, radiotherapy remains the current standard of care for pain palliation in the presence of a fracture or spinal cord compression, explains Kohli. 

Additionally, data from the phase III ALLIANCE A031201 trial were presented at the 2019 ASCO Annual Meeting. Patients with progressive mCRPC were randomized to receive either the combination of enzalutamide (Xtandi) and abiraterone or enzalutamide alone. However, the combination failed to show synergistic activity, concludes Kohli.

Manish Kohli, MD, discusses drugs that have been evaluated in metastatic castration-resistant prostate cancer.

Dr. Kohli on Drugs That Have Been Evaluated in mCRPC

Manish Kohli, MD, vice chair, Department of Genitourinary Oncology, Moffitt Cancer Center, discusses the challenges of molecular classification in prostate cancer.

Predictive pathways in prostate cancer are generally understood. However, applying targeted treatment to individual patients poses an obstacle due to the heterogeneity of the disease, says Kohli. Kohli adds that treatment options pose an added risk of clonal evolution in prostate cancer.

Molecular classification is especially challenging in the metastatic hormone-sensitive setting because patients’ metastatic lesions are not profiled with a biopsy, Kohli says.

In order to overcome these challenges, Kohli’s advice is to look at liquid biopsies of patients in different states of progression, before and after treatment, and within the context of treatment-specific molecular subtypes. From there, personalized treatment may take on a greater role in the field, he concludes.

Manish Kohli, MD, discusses the challenges of molecular classification in prostate cancer.

Dr. Kohli on the Challenges of Molecular Classification in Prostate Cancer

Manish Kohli, MD, vice chair, Department of Genitourinary Oncology, Moffitt Cancer Center, discusses ongoing research with correlative sciences in prostate cancer.

The National Cancer Institute has facilitated bringing correlative sciences into phase II/III trials, says Kohli. Liquid biopsies are becoming an integral aspect of clinical trial designs, he adds. Liquid biopsies can be done with circulating tumor DNA, micro-RNA profiling, or proteomic profiling. As the utility of liquid biopsies continues to be refined, so, too, does the means of collecting and processing blood samples in pre-analytical evaluations. Otherwise, false-positive signatures can result. However, efforts dedicated to standardizing this process are ongoing.

The platforms that are currently being used can vary, says Kohli. Some are designed to evaluate a single signature of a gene, whereas others can evaluate multiple genes at once.

In the post-analytical setting, it can be difficult to know how to translate that information to individual patients. However, that application will help clarify whether a molecular signature is predictive or prognostic for monitoring disease and evaluating minimal residual disease. The data are in early stages of collection, but the work is ongoing, concludes Kohli.

Dr. Kohli Discusses Ongoing Correlative Science in Prostate Cancer

Manish Kohli, MD, vice chair, Department of Genitourinary Oncology, Moffitt Cancer Center, discusses sequencing concerns in metastatic hormone-sensitive prostate cancer (mHSPC).

There are several treatment options available for patients with mHSPC, including docetaxel, apalutamide (Erleada), and abiraterone acetate (Zytiga). Some patients will receive docetaxel within the first 6 months of starting androgen deprivation therapy (ADT). If they progress, they can be re-challenged with docetaxel, or given abiraterone or enzalutamide. On the other hand, if an AR inhibitor is given upfront with ADT and the patient progresses, treatment would be limited to docetaxel, explains Kohli.

It is important to establish the optimal sequencing on an individualized basis, he adds. Access to these agents will also have to be assessed as these drugs are costly. For example, a cost analysis was done between abiraterone and docetaxel in the hormone-sensitive setting, and it was clear that docetaxel is the cheaper option; however, docetaxel is slightly more toxic than abiraterone. These factors will have to be taken into consideration, says Kohli. Biomarkers could help clarify sequencing decisions, but the field has not reached that point yet.

Manish Kohli, MD

Articles

Dr. Kohli on the Use of Enzalutamide and Apalutamide in mHSPC

Dr. Kohli on the Use of Enzalutamide and Apalutamide in mHSPC

Dr. Kohli on Drugs That Have Been Evaluated in mCRPC

Dr. Kohli on the Challenges of Molecular Classification in Prostate Cancer

Dr. Kohli Discusses Ongoing Correlative Science in Prostate Cancer

Dr. Kohli on Sequencing Concerns in Metastatic Hormone-Sensitive Prostate Cancer