Significant extension of progression-free survival with enzalutamide vs. bicalutamide

07.04.2015 18:17

The TERRAIN study compared the effectiveness and tolerability of enzalutamide and bicalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). The first results of the study were presented by Professor Dr. Axel Heidenreich, Aachen, in the late breaking news session at the annual meeting of the European Association of Urology 2015.1 They show a statistically significant extension of progression-free survival with enzalutamide compared to bicalutamide by a median of almost ten months ( 15.7 months vs. 5.8 months, p < 0.0001).

The AFFIRM and PREVAIL studies show that the androgen receptor signaling inhibitor enzalutamide significantly prolongs overall survival and radiographic progression-free survival (rPFS) compared to placebo in patients with mCRPC before and after chemotherapy. In the phase II TERRAIN study, enzalutamide was now compared with bicalutamide.

Primary endpoint of progression-free survival achieved

The study included 375 asymptomatic or mildly symptomatic chemotherapy-naïve patients with mCRPC whose disease progressed despite treatment with an LHRH analogue or after bilateral orchiectomy. They received either 160 mg enzalutamide or 50 mg bicalutamide once daily, each in combination with an LHRH analogue. The primary endpoint of the study was progression-free survival, defined as the time from randomization to radiographic progression, a skeletal-related event, initiation of new antineoplastic therapy, or death, whichever occurred first. Secondary endpoints of the study were PSA response and time to PSA progression. Data cut-off after 240 events for the primary efficacy endpoint was October 2014.

The analysis demonstrated a statistically significant increase in PFS for enzalutamide compared to bicalutamide: The median PFS in the enzalutamide arm was 15.7 versus 5.8 months for bicalutamide - a gain of 9.9 months. The hazard ratio (HR) was 0.44 (95% CI: 0.34-0.57; p<0.0001). The study has therefore reached its primary endpoint.

In addition, the data show a significant advantage of 13.6 months for enzalutamide over bicalutamide in median time to PSA progression (19.4 months vs. 5.8 months; HR 0.28; 95% CI: 0.20 -0.39; p<0.0001). At week 13, 82 percent of enzalutamide patients but only 21 percent of bicalutamide patients achieved a baseline PSA reduction of ≥ 50 percent. The median treatment time for enzalutamide was 11.7 months and 5.8 months for bicalutamide.

“The study shows an improvement for enzalutamide compared to the standard approach - the addition of bicalutamide to LHRH therapy. If the initial results of the TERRAIN study are confirmed, they have the potential to influence the therapeutic landscape of mCRPC," said Heidenreich, who presented initial data from the study during the late breaking news session at the EAU annual meeting in Madrid presented.

The safety profile of enzalutamide in the TERRAIN study is consistent with that of previous studies. No new, previously unknown effects occurred. The most common side effects with enzalutamide were fatigue, back pain, hot flashes and hypertension.

Androgen receptor signaling inhibitor

Enzalutamide, under the trademark XTANDI™, has been indicated since 2013 in adult men with mCRPC who have disease progression during or after docetaxel chemotherapy. The approval was expanded in December 2014: The androgen receptor signaling pathway inhibitor can now also be used to treat men with mCRPC for whom chemotherapy is not yet indicated.