Enzalutamide monotherapy prolongs MFS compared to leuprolide alone in men with high-risk biochemically recurrent PC

Dr Neal Shore - Carolina Urologic Research Center, Myrtle Beach, USA

EMBARK, which we presented at AUA 2023, we published the results in The New England Journal in October of 2023, it was a three-arm trial for patients who had previously undergone either prostatectomy, radiation therapy or both, who had biochemical recurrence but in particular they had PSA doubling times of less than or equal to 9 months. This was a three-arm trial – traditional LHRH with a placebo control and LHRH with enzalutamide, those parts of the study, those two arms, were blinded. A third arm with just monotherapy enzalutamide at 160mg dose, its improved indication in mHSPC, nmCRPC, mCRPC. The bottom line – the study was successful and the FDA expanded the indication for enzalutamide, not just in combination of enzalutamide and LHRH but also enzalutamide monotherapy. So that just expanded the label in November.

At ASCO 2024 I just presented a very interesting aspect of the study because at 36 weeks if your PSA was below 0.2 all three arms got a treatment holiday, an interruption. So we compared the enzalutamide monotherapy arm with the holiday to the LHRH alone. Essentially what we saw was that there was a significant difference in the number of patients who got to the treatment holiday: 25% more in enzalutamide monotherapy than LHRH alone.

At the end of the day, the primary endpoint of the study was metastasis free survival. When we looked at the group that had the holiday, there was really no difference in the MFS if you look at the Kaplan-Meier but if you look at the group that continued through, the enzalutamide monotherapy bested LHRH alone.

So we also had another poster that looked at the combination. The combination, though, was statistically significant, besting lupralide alone with a p-value of 0.003, hazard ratio of 0.47. So now we have, at the end of the day, a really great opportunity for our colleagues to have choices with patients and have shared decision making. For BCR high-risk patients, rapid PSA doubling times, rather than LHRH monotherapy or LHRH alone you can do combination with enzalutamide or enzalutamide by itself and having a discussion regarding the pros and cons of the different adverse event profiles.

What is next for this study?

We have just a lot of data that we’re reviewing. We’ve already presented some of the patient-reported outcome data. We published that in New England Journal Evidence pretty much simultaneously with the New England Journal article of the trial. We’re looking at additional parameters, we’re looking at adiposity of the different arms. We’re also looking at some further analyses of the arm comparisons and a lot of other additional work that we’re doing on trying to delineate some of the adverse event differences as well as sexual function.