Everolimus as first-line therapy in nonrapidly progressive metastatic castration-resistant prostate cancer (mCRPC): A multicenter phase II trial (SAKK 08/08).

4588 Background: Everolimus is a potent, orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) pathway and has shown activity in preclinical cancer models. This phase II study investigated the activity of single agent everolimus as first-line treatment in patients (pts) with mCRPC. Methods: Pts with rising PSA while castrate (testosterone < 50ng/dl) and a PSA-doubling time (PSA-DT) of ≥ 55 days, no prior chemotherapy, and adequate organ function were eligible. Continuation of androgen deprivation therapy was required. Everolimus was administered continuously at a dose of 10mg daily. The primary endpoint was progression free survival (PFS) at 12 weeks defined as absence of PSA increase ≥ 25% over baseline, and no progression of metastases on imaging or clinically. Secondary endpoints included adverse events (AE), PFS, response (PSA, measureable disease), and overall survival. 32 evaluable pts were needed in a Simon's two stage minimax design with a power of 90% and a significance level ...