Overactive.

Top Line: Active surveillance is the preferred treatment for most low-risk and some intermediate risk prostate cancer.

The Study: The whole point of AS is to delay and sometimes avoid treatment and associated side effects without forfeiting clinically meaningful outcomes. So, what if we could give people a pill to delay things even more? If you thought to yourself, why would I take non-curative treatment on AS if the point of AS is to avoid treatment? Such questions don’t usually come up on pharma earnings calls. The phase 2 ENACT trial randomized men undergoing AS for no more than 6 months for low-intermediate risk prostate cancer to either continue AS alone or to the addition of enzalutamide 160 mg daily for one year. The primary outcome was time to pathologic or therapeutic progression. Median time to progression was not met, but over the epic 2 year follow up period, enzalutamide significantly reduced the risk of progression. That benefit was only seen at year 1 where enzalutamide reduced the incidence of progression from 23% to 7.9%. However, there was no difference at 2 years (1 year after stopping enzalutamide) with an incidence of progression of 16% in both arms. Overall, 37.2% experienced progression on AS compared to 28.1% on enzalutamide. That’s right, over a quarter of men still progressed on enzalutamide AS with a <10% absolute reduction in the rate of progression.  The time to progression was “significantly” delayed by 6 months among those who took 1 year of enzalutamide. Over 90% of patients experienced adverse events on enzalutamide including a 55% rate of fatigue and 35%(!) rate of gynecomastia. But take heart, those effects usually improved after stopping therapy.

TBL: A year of enzalutamide for men on AS for low and intermediate risk prostate cancer increases toxicity and reduces the risk of progression at 1 year with no effect on progression after stopping therapy. | Shore, JAMA Oncol 2022