Neal D. Shore, MD, FACS

Neal Shore, MD, FACS the US chief medical officer of Surgery and Oncology at GenesisCare and the director and certified principal investigator at the Carolina Urologic Research Center, discusses results from a post-hoc analysis of the phase 3 ARCHES trial (NCT02677896). The analysis assessed overall survival in patients with prior local therapy, defined as previous radical prostatectomy and/or radiation therapy to the prostate area.

The results were presented during a moderated poster session at the AUA 2022 Annual Meeting, in New Orleans, LA. The analysis demonstrated that enzalutamide (enza; Xtandi) plus androgen deprivation therapy (ADT) improved recurrence-free survival (RFS) and OS vs ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The hazard ratio for the difference between enza plus ADT vs ADT alone was 0.66 (95% CI, 0.53, 0.81; 

According to Shore, in terms of OS and RFS, patients with de novo or recurrent mHSPC did better with the combination, and the positive findings were irrespective of prior treatment with either surgery or radiation, Shore adds.

 I think the most important thing to highlight is that if you have patients who have either de novo mHSPC, or recurrent mHSPC, whether they've had an active treatment for the primary, the prostate, whether it was a surgical extirpation or radiation or both, regardless [of] when they go on to develop metastatic disease.

The patients did remarkably better from an RFS and OS standpoint for those who received combination ADT and enza versus monotherapy ADT.

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Neal Shore, MD, FACS  discusses results from a post-hoc analysis of the phase 3 ARCHES trial.

Long-Term Survival Benefit Shown With Enzalutamide Plus ADT in mHSPC

Neal Shore, MD, the U.S. chief medical officer of Surgery and Oncology, GenesisCare USA, and director, CPI, Carolina Urologic Research Center, discusses an analysis of the relationship between prostate-specific antigen (PSA) response and urinary and bowel adverse events (AEs), time to deterioration in quality of life (QoL), and prostate cancer (PC)–related invasive procedures in the phase 3 ARAMIS clinical trial.

In the study 955 were randomized 2L1 to received darolutamide (Nubeqa) or placebo while continuing androgen deprivation therapy (ADT). Declines in local symptoms were determined using quality of life measurements.

The study ultimately found that treatment with darolutamide correlated with reduction in local urinary and bowel symptoms, as well as delayed deterioration in patient QoL related to urinary and bowel symptoms. There was also a reduction observed in locally invasive procedures following darolutamide treatment.

 ARAMIS was the largest of the very well conducted phase 3 nmCRPC trials, we had 15 109 patients in our study, as with the other two nmCRPC studies, where there was a two to one randomization for nmCRPC patients by conventional imaging, a two to one randomization for patients with receiving an ADT plus darolutamide versus ADT and a placebo. Ultimately, what we were able to demonstrate very successfully was that the metastasis free survival was our primary end point, and that was successful. And then our subsequent secondary endpoints, the first in the hierarchical order was overall survival. And that was also met very successfully. So really, what that has demonstrated in two separate 

 publications is that starting patients on darolutamide, a well described androgen receptor pathway inhibitor, which in preclinical models demonstrates a very minimal amount of blood-brain barrier penetration. I say that because I think that's important regarding it the neuro oncologic tolerability that we see so well with darolutamide. But then, most importantly, [it] not only delayed radiographic progression, it delayed it requirement for anti-neoplastic therapies we saw wonderful PSA responses, PSA 50s [and] PSA 90s, delays in skeletal-related events.

 And now in this particular study, what we've demonstrated is the patients who received darolutamide and as opposed to placebo for nmCRPC had marked improvements in their requirement for locally invasive procedures for urinary symptoms, particularly catheterizations, endoscopic resections, urinary retention, even urinary symptoms of burning frequency urgency, and also we found a decrease in total bowel type symptoms. And these were both evaluated with validated questionnaires. So, I think for my colleagues who are contemplating the decision to start a patient who has an nmCRPC, who's largely asymptomatic, except for the T suppression chronicity, one can comfortably describe to their patient, not only a delay in metastasis-free survival, which was largely driven by radiographic progression, but clearly corroborated with a survival benefit, but now, we're demonstrating improvement in urinary symptoms or avoidance of deterioration of urinary symptoms as well as bowel symptoms.

Neal Shore, MD, FACS, explains the relationship between the use of darolutamide and control of urinary and bowel adverse events, as observed in an analysis of the phase 3 ARAMIS clinical trial. 

Darolutomide Controls Local Symptoms in nmCRPC

Neal D. Shore, MD, FACS, medical director and certified physician investigator at the Carolina Urologic Research Center, discusses the current treatment landscape and upcoming drugs being reviewed by the FDA for the treatment of patients with bladder cancer.

Pembrolizumab (Keytruda) was recently approved in 2020 for patients with persistent carcinoma 

. The FDA will be reviewing 2 intravesical agents, nadofaragene firadenovec (Adstiladrin) and oportuzumab monatox (Vicinium) for potential approval in 2021.

Patients who suffer from high-risk non-muscle invasive bladder cancer and are unresponsive to Bacillus Calmette-Guerin only had the option of having their bladders removed before the approval of pembrolizumab, and hopefully 2 more in 2021, according to Shore.

Shore thinks that the current and upcoming options in this setting are extremely exciting. These options include systemic therapy for metastatic urothelial carcinoma in the bladder, new intravesical treatments for high-risk non-muscle invasive bladder cancer, studies looking at tri-modal bladder-sparing treatments combining neoadjuvant chemotherapy with radiation and immunotherapy, and even the role for immunotherapy checkpoint inhibitors as neoadjuvant strategies. This field continues to evolve at an exponential pace, he says.

Neal D. Shore, MD, FACS, discusses the current treatment landscape and upcoming drugs being reviewed by the FDA for the treatment of patients with bladder cancer.

Current and Upcoming Treatments Provide Options in Bladder Cancer

Neal D. Shore, MD, FACS, medical director and certified physician investigator at the Carolina Urologic Research Center, discusses the results of the retrospective review on real-world patterns of genomic testing in patients with metastatic castration-resistant prostate cancer (mCRPC).

Patients being seen in the community setting made up about 90% of the Flatiron database population used in this analysis, while the other 10% were in the academic setting. Shore and his colleagues looked at about 5000 patients over a several-year period. He says they found that the incidence of patients who were tested in 2013 came to 0% and raised to about 11% by 2018.

Other databases show that the likelihood of homologous recombination repair alteration is about 25% to 30%, which shows a discrepancy in the rate of testing to how many patients are likely to have this alteration, according to Shore. He and his colleagues broke down the most commonly tested gene alterations such as 

This retrospective analysis of a large registry shows that physicians in this field need further education, especially since these alterations have 2 actionable PARP inhibitors approved as of this year, Shore explains.

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Neal D. Shore, MD, FACS, discusses the results of the retrospective review on real-world patterns of genomic testing in patients with metastatic castration-resistant prostate cancer.

Expert Discusses Results of Analysis on Genomic Testing in mCRPC

Neal D. Shore, MD, FACS, medical director, Carolina Urologic Research Center, managing partner, Atlantic Urology Clinics, discusses glypican-1 as a biomarker for prostate cancer.

Glypican-1 is a new receptor found to be involved in many different growth processes of malignant cells, says Shore. It is demonstrable in blood, urine, serum, and plasma. He and his colleagues conducted a preliminary pilot study of 300 patients, and they were able to find a cut point, where they could see a very high specificity for demonstrating patients who had cancer versus those who did not.

Traditionally, other biomarkers have had a fairly high sensitivity for true positives or true negatives, but they do not have the specificity at the same time, adds Shore.

Neal D. Shore, MD, FACS, Atlantic Urology Clinics, discusses glypican-1 as a biomarker for prostate cancer.


Dr. Shore Discusses Glypican-1 as a Biomarker for Prostate Cancer

Neal D. Shore, MD, FACS, medical director, Carolina Urologic Research Center, Myrtle Beach, on the utility of the androgen receptor inhibitor ODM-201 for the treatment of castration-resistant prostate cancer (CRPC).

In phase I and II multinational trials, favorable results have been observed regarding PSA kinetics modulation

The organic structure of ODM-201 seems to cause the agent to have a much lower penetration through the blood-brain barrier

The efficacy of ODM-201 is being measured in terms of its impact on radiographic disease, PSA, and the androgen receptor

ODM-201 has been studied in patients prior to and following chemotherapy, as well as in patients who have and have not received abiraterone

Additional trials are being planned to analyze safety, efficacy, and tolerability

ODM-201 will be studied in a large trial of non-metastatic patients

Neal D. Shore, MD, FACS | Authors

Articles

Long-Term Survival Benefit Shown With Enzalutamide Plus ADT in mHSPC

Darolutomide Controls Local Symptoms in nmCRPC

Current and Upcoming Treatments Provide Options in Bladder Cancer

Expert Discusses Results of Analysis on Genomic Testing in mCRPC

Dr. Shore Discusses Glypican-1 as a Biomarker for Prostate Cancer

The Utility of ODM-201 in CRPC