Dr. Morgans on real-world study comparing darolutamide, enzalutamide, and apalutamide in nmCRPC

Alicia Morgans, MD, genitourinary medical oncologist, Dana-Farber Cancer Institute, discusses the retrospective DEAR trial, a comparative real-world dana analysis of outcomes in patients with nonmetastatic castration-resistant prostate cancer initiating their first androgen receptor inhibitor treatment with darolutamide (Nubeqa), enzalutamide (Xtandi), or apalutamide (Erleada). Morgans shared these findings at the 2023 ASCO Annual Meeting.¹

Video Transcription

We performed this study by using a network of electronic medical records through the PPS network of US urology practices. And we identified patients who had nonmetastatic castration-resistant prostate cancer who were being treated in those centers between August 1, 2019 and March 31, 2022. And within that, we then tried to identify from an index period of starting either darolutamide, enzalutamide, or apalutamide for their nonmetastatic CRPC, how long they were undergoing treatment with those particular agents, and what happened to them during treatment—whether they needed to discontinue the treatment, whether they continued on therapy, whether they had cancer progression, whether they had adverse events—to try to kind of get a picture, again, within a real-world setting, of how these medications were being used and how patients were faring.

We had in this analysis 870 patients with nonmetastatic CRPC. And what we found was that in analyses both unadjusted and adjusted, patients seemed to discontinue their enzalutamide and apalutamide at slightly earlier time points than their darolutamide across a longitudinal follow-up. So the hazard ratio in the adjusted analysis for discontinuation of darolutamide versus enzalutamide was 0.726, suggesting a longer time to discontinuation on darolutamide. And when we compare darolutamide to apalutamide in an adjusted analysis, the hazard ratio for discontinuation was 0.609, again, favoring darolutamide in terms of longer time to discontinuation.

When we thought about why patients were discontinuing therapy, of course, we thought about disease progression, adverse events, or other things that might be contributing to that. And we tried to understand and analyze what the reasons were for this. Now, we did have the analysis of charts by practitioners in these practices. So it was very lucky that we could try to get some understanding of not only what was happening, but also why. And in this, we saw that the most common reason for discontinuation of therapy within this dataset was adverse events. And the rate of adverse events was somewhat lower numerically among patients treated with darolutamide, in terms of a reason for discontinuation, than it was for enzalutamide and apalutamide, again, as a reason for discontinuation. So this doesn't characterize and quantify every single adverse event that was happening to these patients, but in the context of discontinuation, these rates were numerically different.

There were also lower rates, in terms of reasons for discontinuation, for progression to metastatic CRPC for patients who were treated with darolutamide when compared with those patients treated with enzalutamide and apalutamide. This is a numeric comparison, there was not a statistical test performed to actually formally compare these though. And other reasons for discontinuation included switching to another androgen receptor signaling inhibitor or cost reimbursement factors and then a bundle of other things that were just sort of characterized as other or unknown.

We eventually looked deeper into the data on progression to metastatic CRPC and we saw that the proportion of patients with progression to mCRPC was lower among patients treated with darolutamide than among patients treated with apalutamide or enzalutamide when we conducted a formal statistical comparison with both unadjusted and adjusted analyses.

Transcription has been edited for clarity.

Reference

1. Morgans AK, Shore ND, Khan N, et al. Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR. J Clin Oncol 41, 2023 (suppl 16; abstr 5097). doi: 10.1200/JCO.2023.41.16_suppl.5097