Enzalutamide tied to better outcomes than bicalutamide in mHSPC

A regimen comprising enzalutamide and androgen deprivation therapy (ADT) led to better outcomes compared with a bicalutamide-ADT regimen in an earlier setting of metastatic hormone-sensitive prostate cancer (mHSPC), particularly in Black men, a phase II study suggests.

Several pivotal trials have reflected the benefit of early intensification of mHSPC therapy by adding an ARAT* agent; however, the study populations were predominantly White. [N Engl J Med 2017;377:338-351; N Engl J Med 2019;381:13-24; N Engl J Med 2019;381:121-131; J Clin Oncol 2019;37:2974-2986] “PC has a higher mortality rate among Black than White men, [but] Black patients are grossly underrepresented in prospective trials of advanced PC,” said the researchers.

“Enzalutamide demonstrated a greater magnitude of improvement over bicalutamide in terms of the rate and duration of PSA** response in Black patients [with mHSPC],” they continued.

Seventy-one men (median age 65 years, 41 percent Black) were randomized 1:1 to receive daily oral enzalutamide 160 mg or bicalutamide 50 mg on top of LHRH*** analogue therapy. Of these, 26 men had bone pain (tied to shorter survival in advanced PC) while 37 had extensive disease (≥4 metastatic lesions). Seven-month PSA response (SMPR) rate, recognized as a surrogate for overall survival (OS) in mHSPC, was the study’s primary endpoint. [JAMA Network Open 2021;4:doi:10.1001/jamanetworkopen.2020.34633]

Compared with bicalutamide recipients, more men on enzalutamide achieved the SMPR rate (94 percent vs 65 percent; p=0.008). A subset analysis on Black men revealed a similar trend (93 percent vs 42 percent; p=0.009).

PSA response rate remained better with enzalutamide vs bicalutamide at 12 months (84 percent vs 34 percent).

Despite the significant improvements in TTPP^# (hazard ratio [HR], 0.15; p<0.001) and OS (HR, 0.31; p=0.002) with enzalutamide vs bicalutamide, these data were immature at the time of evaluation.

The incidence of grade 3 adverse events (AEs) deemed clinically relevant or related to therapy was similar between the enzalutamide and the bicalutamide arms (n=7 vs 5). The most common AEs associated with enzalutamide use were hypertension and syncope (n=3 and 2, respectively). One enzalutamide recipient discontinued owing to a seizure. No grade 4/5 treatment-related AEs, unexpected AEs, or deaths were reported, suggesting that enzalutamide was well-tolerated.

“[Our findings imply that bicalutamide-ADT] is an inadequate therapy in all cases … especially for Black patients … [Our] study confirms that racial differences in bicalutamide efficacy are overcome by using contemporary ARAT such as enzalutamide in advanced PC,” the researchers explained.

However, due to the improved OS observed with abiraterone and prednisone in one trial, [N Engl J Med 2017;377:352-360] the researchers noted that they “could no longer ethically randomize patients to bicalutamide … [We had] to administratively close the study to accrual slightly short of the target sample size … [Nonetheless,] the impact of that decision on our results and conclusions is minimal, and any small loss of statistical power is unimportant because a significant difference in favour of enzalutamide was still observed.”

Also, despite the immature TTPP and OS data, the prospective design and race stratification with nearly half of the population being Black cumulatively render the conclusions “meaningful for clinical application”.

“[As such,] the favourable risk-benefit profile [of enzalutamide] makes it crucial to strongly consider … incorporating it in the mHSPC treatment plan,” they concluded.