by ecancer reporter Janet Fricker

Enzalutamide (XTANDI) in comparison to bicalutamide in combination with an LHRH analogue delivered improvements in progression free survival (PFS) for patients with metastatic castration-resistant prostate cancer (MCRPC), reported the phase 2 TERRAIN trial at the 2015 European Association of Urology (EAU) Congress in Madrid, Spain, 20th - 24th March.

Furthermore, the phase 3 PREVAIL study, reported at the same meeting, showed enzalutamide in comparison to placebo improved survival in chemotherapy-naïve MCRPC patients.

Enzalutamide, approved by the EMA in June 2013, is a rationally designed, targeted androgen-receptor inhibitor that competitively binds to the ligand-binding domain of the androgen receptor and inhibits androgen-receptor translocation to the ligand-binding domain of the androgen receptor, androgen-receptor translocation to the cell nucleus, recruitment of cofactors, and androgen-receptor binding to DNA.

It is believed that enzalutamide may offer particular benefit to men with castration-resistant prostate cancer.

For the TERRAIN study, presented by Axel Heidenreich, from University Hospital Aachen, Germany, 375 patients with metastatic prostate cancer whose disease had progressed despite treatment with luteinizing hormone-releasing hormone (LHRH) analogue therapy or surgical castration were randomised to enzalutamide at a dose of 160 mg taken orally once daily or bicalutamide at a dose of 50mg taken once daily in combination with an LHRH analogue.

Results showed median progression free survival was 15.7 months in the enzalutamide arm compared to 5.8 months in the bicalutamide plus LHRH analogue arm (HR 0.44, 95% CI 0.34-0.57; p<0.0001).

Furthermore, median time to PSA progression was 19.4 months with enzalutamide versus 5.8 months with bicalutamide plus LHRH analogue (HR 0.28, p<0.0001).

Serious adverse events were reported in 31.1 % of enzalutamide patients versus 23.3% of bicalutamide patients, and Grade 3 or higher cardiac adverse events were observed in 5.5% of enzalutamide patients versus 2.1% of bicalutamide patients.

“The results of the TERRAIN trial, if confirmed, have the potential to impact the treatment landscape of metastatic castration-resistant prostate cancer,” said Heidenreich.

“The study demonstrated an improvement with enzalutamide over the standard practice of the addition of bicalutamide to LHRH therapy.”

For the PREVAIL trial, presented by Bertrand Tombal, from Saint-Luc University Hospital, Brussels, 1,717 patients with chemotherapy-naïve metastatic prostate cancer whose disease had progressed on androgen deprivation therapy were randomised to enzalutamide (n=872) or placebo (n=845).

The updated overall survival analysis conducted at 784 deaths found a statistically significant overall survival benefit for the enzalutamide arm (HR 0.77; 95% CI 0.67-0.88; p=0.0002).

“The study demonstrates that starting patients on enzalutamide at the point when their castration-resistant prostate cancer becomes metastatic has the potential to prolong survival,” said Tombal, adding that the standard approach has been to wait for symptoms or rapid radiological progression before initiating chemotherapy.

“The overall survival analysis from the PREVAIL trial confirms significant overall survival benefit despite many patients receiving subsequent treatments.”

References

'A randomized double-blind phase 2, efficacy and safety study of enzalutamide vs. bicalutamide in metastatic castrate resistant prostate cancer.' TERRAIN trial. Abstract presented at EAU 2015.

'Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): Final overall survival analysis of the phase 3 PREVAIL study.' Abstract presented at EAU 2015.