Sponsored Content: Neal Shore, MD, FACS reviews new data on the TITAN trial of apalutamide in patients with mCSPC.

Understanding Efficacy, Safety, and PSA Kinetics of Apalutamide Plus ADT in Patients With Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

This content is not certified for continuing education. The speaker has been compensated by Janssen Biotech, Inc.

Videos

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses the approval of relugolix (Orgovyx) in advanced prostate cancer. 

On December 18, 2020, the FDA approved relugolix, a gonadotropin-releasing hormone receptor antagonist, for the treatment of patients with advanced prostate cancer. 

The approval is based on findings from the phase 3 HERO trial, in which relugolix demonstrated superior sustained testosterone-suppression through 48 weeks, fast testosterone recovery after discontinuation, and a 50% reduction in major adverse cardiovascular events compared with leuprolide (Lupron) in this patient population.

According to Shore, the ability to offer patients an additional treatment option is welcomed. 

Moreover, oral agents such as relugolix have the potential to spare patients mandatory trips to the clinic, says Shore. Additionally, treatment with relugolix may minimize the risks associated with receiving treatment in person, particularly given the coronavirus disease 2019 pandemic.

Additionally, relugolix may be a convenient option for patients as it is a once-a-day regimen where patients see their urologist, medical oncologist, or radiation oncologist when clinical evaluation is warranted, concludes Shore.

Neal D. Shore, MD, FACS, discusses the approval of relugolix in advanced prostate cancer.  

Dr. Shore on the FDA Approval of Relugolix in Advanced Prostate Cancer 

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses the need for further education on molecular testing for metastatic castration-resistant prostate cancer (mCRPC).

The field of prostate cancer has begun to adopt the 2017 National Comprehensive Cancer Network (NCCN) molecular testing for homologous recombination repair (HRR) gene alteration guidelines, says Shore. During the

, a retrospective review of the large US Flatiron Health database was presented. Results demonstrated only a modest increase of testing for HRR alternations in patients with mCRPC after 2017 when the NCCN recommendations were changed. Part of that is based upon a need for additional education on the differences between both germline versus somatic testing, according to Shore.

The utility for finding someone with an HRR mutation is necessary now that PARP inhibitors have been approved, explains Shore. There are other gene alterations where checkpoint inhibitors may be of value, particularly when there are tumor agnostic findings. As the field continues to evolve, there is a need for additional education across all specialties, including medical oncology, urology, and radiation oncology, concludes Shore.

Neal D. Shore, MD, FACS, discusses the need for further education on molecular testing for metastatic castration-resistant prostate cancer.

Dr. Shore on the Need for Further Education on Molecular Testing in mCRPC

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses unique challenges in nonmetastatic castration-resistant prostate cancer (CRPC). 

In clinical trials, survival is used to determine an agent’s utility in nonmetastatic CRPC, explains Shore. 

This is largely due to the fact that patients with nonmetastatic disease are often asymptomatic, regardless of tumor burden, says Shore. Moreover, these patients do not typically have a high tumor burden and instead have microscopic disease. 

Although chronic androgen deprivation therapy use may lead to adverse effects (AEs), rising prostate-specific antigen and suppressed testosterone levels remain the main concerns in this patient population, Shore explains. 

 showed that darolutamide (Nubeqa) significantly improved metastasis-free survival and overall survival without inducing significant AEs compared with placebo, concludes Shore. 

Neal D. Shore, MD, FACS, discusses unique challenges in nonmetastatic castration-resistant prostate cancer.  



Dr. Shore on Unique Challenges in Nonmetastatic CRPC 

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses the cardio-oncology strategies that can be implemented in patients with prostate cancer to reduce the chances of a cardio-related adverse-event.

The whole field of cardio-oncology across different disease states has gotten more traction, says Shore. When testosterone suppression is given, a quasi metabolic syndrome is created where central adiposity is seen along with arrhythmia and QT prolongation; this potentially occurs with LHR antagonists. While these adverse effects (AEs) are not see with relugolix (Relumina), it is still important to make sure that patients are following a heart healthy diet, regularly exercising, and having their lipid panels and cholesterols checked. If the patient has diabetes, it is important that they are under tight glucose management, thattheir hemoglobin A1C is carefully monitored, as well as avoiding smoking or a sedentary lifestyle. These are the classic outlines that patients can follow to decrease the chances of a cardiac event.

The phase 3 HERO trial is a prime example of this because it adds to a strategy of avoiding cardiovascular toxicity and at the same time achieving rapid T-suppression and PSA corollary declines. There were also excellent results in the T levels that went below 20 ng/dL, although <50 ng/dL is the pharmacologic endpoint for approval. The field can be a lot more proactive with cardio-oncology strategies, as well as with prostate cancer therapeutic selections, concludes Shore.

Neal D. Shore, MD, FACS, discusses the cardio-oncology strategies that can be implemented in patients with prostate cancer to reduce the chances of a cardio-related adverse-event.

Dr. Shore on Cardio-Oncology Strategies in Prostate Cancer

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses the safety profiles of relugolix (Relumina) and leuprolide (Lupron) in advanced prostate cancer.

While testosterone suppression can reduce cancer cell proliferation, it is associated with significant toxicity, says Shore. Moreover, cardiovascular events are of particular concern among elderly men with prostate cancer.

Regarding safety from the phase 3 HERO study presented at the 2020 ASCO Virtual Scientific Program, cardiovascular events occurred in 7.1% of patients who were treated with leuprolide versus 3.9% of patients treated with relugolix. Additionally, major adverse cardiovascular events (MACEs) were observed in 6.2% and 2.9% of patients, respectively.

Ultimately, relugolix was found to induce a 54% reduction in the risk of MACEs compared with leuprolide among patients with advanced prostate cancer, concludes Shore.

​Neal D. Shore, MD, FACS, discusses the safety profiles of relugolix and leuprolide in advanced prostate cancer.



Dr. Shore on the Safety Profiles of Relugolix and Leuprolide in Prostate Cancer

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Institute, discusses immunotherapy targeting prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in biochemically recurrent prostate cancer.

Previously, investigators evaluated INO-5150, a DNA-based immune therapy that targets PSA and PSMA with or without plasmid-encoded cytokine adjuvant interleukin-12 (INO-9012) in a phase 1/2 trial. The treatment was well-tolerated and safe, with no treatment-related serious adverse events. In an analysis that was presented at the 2020 AACR Virtual Annual Meeting II, INO-5150 with or without INO-9012 was administered followed by electroporation with CELLECTRA® on day 0, and weeks 3, 12 and 24. Peripheral blood mononuclear cells were collected before and after treatment from a subset of patients (n=19) and stimulated with PSA or PSMA peptides, negative or positive controls.

Treatment with INO-5150 with or without INO-9012 drove the expansion of antigen specific T cells. Patients with immune reactivity by flow cytometry were more likely to have a higher frequency of PSA/PSMA specific T-cell receptors (TCRs) that expanded at least 10-fold over their pretreatment value. However, patients without immune reactivity also demonstrated expansion in TCRs. The results suggest that INO-5150 induced PSA/PSMA specific T cells and that TCR sequencing is a valuable tool for assessment of immune responses induced by immunotherapy. Although the approach may not be a full-proof way to avoid T-cell suppression, it could help delay the time to androgen deprivation therapy, concludes Shore.

Neal D. Shore, MD, FACS, discusses immunotherapy targeting prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) in biochemically recurrent prostate cancer.

Dr. Shore on Immunotherapy Targeting PSA and PSMA in Biochemically Recurrent Prostate Cancer

Neal D. Shore, MD, FACS, medical director of the Carolina Urologic Research Center, discusses the rationale for conducting the phase 3 HERO trial in advanced prostate cancer.

At the 2020 ASCO Virtual Scientific Program, findings from the HERO trial showed that relugolix (Relumina) given as once daily oral therapy was superior to leuprolide (Lupron) in terms of sustained castration rates, prostate-specific antigen response, and testosterone recovery.

Additionally, the agent led to a 54% decrease in the likelihood of major adverse cardiovascular events compared with leuprolide.

Relugolix is a gonadotropin-releasing hormone (GnRH) receptor antagonist that can prevent testosterone surge and clinical symptom flare, explains Shore. Moreover, GnRH antagonists appear to have a superior mechanism of action compared with traditional luteinizing hormone-releasing hormone receptor agonists.

On June 22, 2020, the FDA granted a priority review designation to a new drug application for relugolix as a treatment for patients with advanced prostate cancer, according to data from the HERO trial.

​Neal D. Shore, MD, FACS, discusses the rationale for conducting the phase 3 HERO trial in advanced prostate cancer.



Dr. Shore on the Rationale for the Phase 3 HERO Trial in Advanced Prostate Cancer

Neal Shore, MD, the medical director of Carolina Urologic Research Center, discusses the role for abiraterone in patients with chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC).

The elderly population can be immunocompromised, worsening fatigue, more deconditioning, and they are often already on androgen deprivation therapy (ADT), says Shore.

When selecting therapy, it is important not to exasperate issues that may already exist in elderly patients like fatigue, lack of appetite, or their diminished participation in extracurricular type activities, specifically their physician activity. Some elderly patients may also have challenges in cognitive function. Abiraterone is very safe and well-tolerated in that patient population of elderly patients, says Shore.

Neal D. Shore, MD, FACS

Articles