Continuing Darolutamide Does Not Increase Adverse Events in nmCRPC

Neal Shore, MD, the United States chief medical officer of surgery and oncology at GenesisCare, and the director and certified principal investigator at the Carolina Urologic Research Center, discusses the long-term exposure analysis of darolutamide (Nubeqa) in the phase 3 ARAMIS Rollover trial (NCT04464226) for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

Patients were permitted to continue with darolutamide after the ARAMIS study (NCT02200614); 294 (31%) patients entered the rollover study. Thirty percent of these patients received darolutamide for at least 4 years; results of this trial were presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).

Investigators performed an analysis of exposure-adjusted incidence rate of treatment-emergent adverse events (AEs) of special interest for darolutamide. These included fatigue, fall, rash, fracture, mental impairment, and hypertension. Shore says that incidence of these AEs in all patients who received darolutamide was all in the single digits beside fatigue, at 14.3%. In the patients who continued in the rollover study, fatigue only increased slightly, to 14.9%, and the same was true of other AEs. The exposure-adjusted incidence rate for these AEs was the same or lower for the rollover study patients who received darolutamide for over 4 years.

Shore says that this shows patients can receive an androgen receptor therapy in the long term without causing added toxicity besides T-cell suppression, which is important as patients with nmCRPC tend to be older.

TRANSCRIPTION:

0:08 | We also looked at exposure, and one of the ways that we looked at is an exposure-adjustment analysis, where we looked at fatigue, fall, fracture, rash, mental impairment, hypertension—the types of [AEs] that are often seen throughout the class of androgen receptor signaling inhibitor drugs. What we found, and this is in our poster presented at ASCO GU 2023, that this incidence was not only very low—essentially single digit [percentage], with the exception of slightly above that for fatigue at 14%—but virtually single digits in fall, fracture, rash, and mental impairment disorder not only for the original trial presentation in our first publication, but now in this rollover for the 30% of patients staying on drug out to north of 4 years, a minimal increase in those percentages of AE experiences.

1:24 | So I think this…should be very reassuring to patients, who tend to be elderly, who have nmCRPC. By elderly, usually, the average age is over 70 [years] in these studies. But [it should be] also reassuring to physicians that we're starting patients on a therapy that, other than having the [AEs] of T suppression, they typically are not having any other [AEs] because they don't have any demonstrable tumor burden on conventional imaging. So therefore, adding another drug, like darolutamide, overall, has demonstrated in long term in this rollover, its safety profile.