There is still a role for first generation antiandrogens (FGAs) in the management of metastatic castration-resistant prostate cancer (mCRPC), according to an Australian study.
Importantly, the use of agents such as bicalutamide does not impact the efficacy of subsequent systemic therapies while a PSA50 response to FGA treatment is a significant favourable prognostic marker.
The retrospective, multicentre cohort study comprised 634 patients from 11 sites enrolled in the electronic CRPC Australian Database (ePAD) between 2016 and 2019.
During a median follow-up of 21.9 months, half the patients (51%) had received FGAs as initial therapy after diagnosis of castration resistance.
Among the FGA treated patients, 37% achieved a PSA50 response, 20% had a PSA response of <50% compared to baseline levels, and 43% had no PSA response.
“Patients treated with FGAs had significantly longer OS compared to those who did not receive FGAs (HR 0.516, 95% CI 0.368–0.724; P < 0.001).”
“Among those who received FGAs, patients with a PSA50 response had significantly improved OS compared to those without biochemical response and those with a PSA response of <50%,” the study said.
On multivariate analysis, a PSA50 response to FGA remained a favourable independent prognostic factor (HR 0.232, 95%CI 0.112–0.482; <0.001), as well as higher PSA-doubling time of >3 months (HR 0.3675; 0.199–0.672; P = 0.001).
The study, published in BJUI International, said there were no significant differences in the proportion of patients who received subsequent systemic therapy based on prior FGA use, nor in the treatment choice following FGA therapy.
“The most common systemic therapy received in the first-line setting was enzalutamide (38% in both groups), followed by docetaxel (30% vs 24% in those who did and did not receive prior FGA, respectively).”
“Similarly, the PSA50 response rates to any subsequent first-line systemic therapies did not differ based on previous FGA use, including with enzalutamide (51% vs 59%, P = 0.36), abiraterone acetate (51% vs 42%, P = 0.65) or docetaxel (54% vs 48%, P = 0.84).”
The investigators, including Associate Professor Ben Tran from the Peter MacCallum Cancer Centre, noted that patients treated with FGAs were more likely to have lower ISUP grade group at diagnosis, longer time to development of CRPC, and lower incidence of visceral metastases.
“This supports the suggestion that FGAs are often used as an initial therapy in lower-risk patients given their favourable side-effect profile, despite reduced efficacy compared to newer systemic therapies,” the investigators said.
They said the higher rate of cardiovascular risk factors among patients treated with FGAs may reflect a preference to use FGAs rather than novel antiandrogens in those with significant pre-existing comorbidities.
European Association of Urology guidelines suggest there is no role for FGAs after the development of CRPC, they noted.