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ORLANDO -- PSA progression slowed significantly in prostate cancer patients switched to degarelix (Firmagon) after 12 months of leuprolide therapy, data from an open-label extension study showed.

The hazard ratio for PSA progression-free survival (PFS) declined from 0.20/events/year after 12 months of leuprolide to 0.08 after another year of treatment with degarelix (P=0.003), according to a presentation here at the Genitourinary Cancers Symposium.

The extension data also showed that degarelix was associated with a significant increase in the interval before 25% of patients had had PSA failure or death.

"These data support the durability of the significant PSA progression-free survival benefit of degarelix over leuprolide occurring [during randomized treatment]," said Neal Shore, MD, of Carolina Urologic Research Center in Myrtle Beach, S.C. "The data also support the use of degarelix as first-line androgen deprivation therapy."

The findings came from an open-label extension of a phase III pivotal trial comparing degarelix and the LH-RH agonist leuprolide.

The primary results showed significant advantages for degarelix in terms of speed of androgen and PSA suppression, risk of PSA failure or death, and reduced levels of a biomarker associated with metastatic disease (BJU Int. 2008;102:1531-1538, Eur Urol. 2010;57:836-842, BJU Int. 2010;106:182-187).

The trial compared treatment with leuprolide 7.5 mg or degarelix at a starting dose of 240 mg, followed by randomization to a maintenance dose of 80 or 160 mg for 12 months.

At the end of randomized therapy, patients in the degarelix groups had the option to continue maintenance treatment with their randomized dose. Patients initially treated with leuprolide could switch to degarelix, beginning with 240 mg and then random assignment to the maintenance doses.

Shore reported data from a median follow-up of 27.5 months and included only the 80-mg degarelix group, which is the approved dose. The primary endpoint was PSA-PFS, defined as at least a 50% increase from baseline on two occasions two weeks apart and a PSA value ≥5 ng/mL.

Both the overall analysis and a subgroup analysis of patients with PSA values ≥20 ng/mL showed significant slowing of PSA progression in men who switched from leuprolide to degarelix (P=0.003, P=0.031). PSA values remained stable among patients initially randomized to degarelix.

In the randomized phase of the study, treatment with degarelix was associated with a trend toward a longer interval until 25% of patients had PSA progression or died. Subgroup analysis showed the between-group difference achieved statistical significance in patients who had baseline PSA values ≥20 ng/mL.

Carrying the analysis of time to 25% PSA failure/death into the extension phase, investigators found that the difference in favor of degarelix had increased with additional following. Among patients with baseline PSA values ≥20 ng/mL, the difference had increased from about 100 days at the end of randomized treatment to more than 200 days (P=0.01).

Invited discussant Michael Morris, MD, of Memorial Sloan-Kettering Cancer Center in New York City, pointed out that exclusion of the 160-mg degarelix group has muddled analyses of the study. Patients randomized to the higher maintenance dose did no better than the patients treated with leuprolide.

"If you incorporated all of the patients treated with degarelix and compared them to the leuprolide arm, you would see a reduction in the difference in progression-free survival of 35%; you would lose 35% of your effect," said Morris.

"Whether that would still be statistically significant, I don't know. But I do think all of the data need to be presented for all of the patients who were treated with degarelix."

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