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Darolutamide demonstrates high overall survival benefit and safety in non-metastatic CRPC


Findings of a recent study show that patients with non-metastatic castration resistant prostate cancer (nmCRPC) who have multiple comorbidities respond well to the androgen receptor pathway drug darolutamide (Nubeqa). This study was presented at the 2022 ASCO Genitourinary Cancers Symposium.1

Neal D. Shore, MD

Neal D. Shore, MD

Neal D. Shore, MD, FACS, discusses the findings further in an interview with Urology Times. He emphasizes the prolonged survival that patients with nmCRPC experienced with combination therapy and why more urologists should be “proactive” when developing plans of treatment for patients with this disease. Shore is the director of the Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, South Carolina.

Please discuss the background for the study.

The ARAMIS trial was 1 of 3 trials in the non-metastatic castration resistant prostate cancer landscape, or the patients who [we] previously called M0 CRPC. I think most would agree that non-metastatic castration-resistant prostate cancer is a better description. Some have said [these are] really patients who have micro metastatic disease as opposed to macro metastatic disease, or mCRPC, based upon conventional imaging. Conventional imaging [refers to] traditional multi-slice CT scans and technetium bone scans. Really, what the ARAMIS trial [NCT02200614] had previously demonstrated was, first, a marked delay in radiographic progression to the tune of nearly 2 years. And then ultimately, these same patients also had a statistically significant, greater-than-a-year improvement in survival despite crossovers. What we wanted to further review—and certainly, [we] applaud the leadership of all of the investigators, Karim Fizazi, MD, PhD, and the leadership at Bayer—was taking a long-term view about not only the efficacy, but also the safety for patients, given a plethora of comorbidities that many of these elderly patients have.

What were the notable findings of this study? Were any of them surprising to you or your co-authors?

I think it's really interesting to observe that patients who move further along in their prostate cancer journey, naturally—not surprising—tend to be older. So, more than 50% of the patients in the ARAMIS trial, which was a very significant number of patients—north of 1500 patients—had a minimum of 6 or more comorbidities of significance. Typically, [they were] cardiovascular, and other types of comorbidities that we see in elderly patients. I think the median age for this population was about 74. Remarkably so, we see the presence of polypharmacy, [where] more than 50% of the patients were on, believe it or not, 10 or more daily medications. I think that was surprising to some, not to others. But it just speaks to the complexity of the health index for these patients.

How will these findings impact the way that you treat prostate cancer in the future?

I think what we're showing here is that the overall survival benefit, as well as the safety analysis, regardless of the number of comorbidities, was rather significant. The number of concomitant medications, [or] the attendant drug-drug interactions that we have to be careful for, and the potential compounding of safety and tolerability was consistent. There was no significant discrepancy of any type, regardless of the number of concomitant medications [or] the number of comorbidities in this elderly population. Patients, regardless, did markedly better specifically for their survival and disease progression, and [tolerated] the therapy very well compared to the placebo control arm.

What is the take-home message for the practicing urologist?

The take-home message is that we historically have said, "First do no harm," but I think when we can provide benefit and safety concomitantly, that's our North Star. I think oftentimes in elderly patient populations with advanced cancer—[in this case,] non-metastatic CRPC—many patients and their caregivers and health care providers alike, whether they're a medical oncologist, urologist, [or] radiation oncologist, may say, "Well, I want to wait until I see more tumor burden." That's clearly not the right way to think. I say that because this long-term data suggests that these patients not only have prolonged survival when [the] combination with darolutamide is added in nmCRPC patients, [but they also] clearly did better than the control placebo arm. Both arms had testosterone suppression ADT, [and] they tolerated overall very well.

Is there anything else you feel our audience should know about this topic?

I think we're continuing to learn a lot of different things about the androgen receptor pathway drugs, clearly survival prolongation, preservation of quality of life, [and] prevention of complication of therapy, while in the setting of understanding a patient's risk tolerance or their preference value. I think this data is very compelling to merely have our colleagues say, "Wait a second, I can augment your therapy." It's not just sitting back and responding reactively, but [being] proactive by adding an oral medication that, for the most part, is very well tolerated and life prolonging.


1. Fizazi K, Shore ND, Smith MR, et al. Efficacy and safety outcomes of darolutamide in patients with nonmetastatic castration-resistant prostate cancer with comorbidities and concomitant medications from ARAMIS. Paper presented at: 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; San Francisco, California. Abstract #256

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