Enzalutamide may improve PSA remission, survival rates in prostate cancer
Enzalutamide may improve the rate of achieving prostate-specific antigen (PSA) remission and consequently, survival outcomes among prostate cancer patients, according to studies presented at the ASCO Genitourinary (ASCO GU) Cancers Symposium 2018.
In a randomized trial evaluating 71 men (median age 67 years) with metastatic hormone-sensitive prostate cancer, researchers compared enzalutamide against bicalutamide in combination with androgen deprivation therapy (ADT) using luteinizing hormone-releasing hormone. PSA was monitored monthly for the first 7 months and every 3 months thereafter. [ASCO GU 2018, abstract 190]
At 7 months, PSA nadir <4 ng/mL was achieved by nearly all enzalutamide recipients (96.3 percent), outdoing the 66.7-percent rate in the bicalutamide arm.
Additionally, 6-month PSA remission rates at 7 months were 86.0 percent and 79.0 percent in the enzalutamide and the bicalutamide arms, respectively.
Another study known as the PROSPER* trial also demonstrated improved survival rates with enzalutamide among men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). In this study, 1,401 participants were randomized 2:1 to receive enzalutamide 160 mg or placebo. Median treatment duration was 18.4 and 11.1 months, respectively. [ASCO GU 2018, abstract 3]
Compared with placebo, enzalutamide significantly prolonged median metastasis-free survival (36.6 vs 14.7 months, hazard ratio [HR], 0.29, 95 percent confidence interval [CI], 0.24–0.35; p<0.0001), time to first use of new antineoplastic therapy (39.6 vs 17.7 months, HR, 0.21, 95 percent CI, 0.17–0.26; p<0.0001), and time to PSA progression (37.2 vs 3.9 months, HR, 0.07, 95 percent CI, 0.05–0.08; p<0.0001).
Interim median OS analysis also demonstrated a trend favouring enzalutamide over placebo (HR, 0.80, 95 percent CI, 0.58–1.09; p=0.1519).
“Men with M0 CRPC and rapidly rising [PSA] are at high risk of developing metastatic (M1) CRPC … [Our findings revealed] a clinically meaningful and statistically significant 71 percent reduction in the risk of developing M1 CRPC,” said the PROSPER investigators.
In terms of safety outcomes however, two studies suggested higher incidences of adverse events (AEs) associated with enzalutamide use.
In the multicentre, phase IV, prospective REAAcT** study conducted on 92 evaluable participants (median age 75 years) with metastatic castration-resistant prostate cancer, enzalutamide use resulted in a 52-percent AE rate as opposed to the 36-percent rate with abiraterone acetate with prednisone (AAP). Fatigue-related AEs were also higher with enzalutamide vs AAP (26 percent vs 8 percent). [ASCO GU 2018, abstract 296]
The PROSPER study also revealed higher AE rates with enzalutamide vs placebo (any grade, 87 percent vs 77 percent; grade ≥3, 31 percent vs 23 percent; serious, 24 percent vs 18 percent), with 10 percent of enzalutamide recipients discontinuing treatment due to AE.
Nonetheless, the PROSPER researchers acknowledged that their findings were consistent with the established safety profile of enzalutamide despite the higher AE rates.