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.
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.
0:07 | 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 New England Journal [of Medicine] 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.
1:59 | 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.