A Phase 3 Study to Evaluate the Efficacy and Safety of Docetaxel and Prednisone (DP) with or without Lenalidomide (LEN) in Patients with Castrate-Resistant Prostate Cancer (CRPC): The Mainsail Trial

ABSTRACT Introduction LEN, an antiangiogenic and immunomodulatory agent was active and well tolerated as a single agent and in combination with DP in phase 1/2 trials in CRPC. This phase 3, multicenter, randomized, double-blind, placebo (PBO)-controlled study evaluated the efficacy and safety of LEN versus PBO in combination with DP as first-line treatment for CRPC. Methods Chemotherapy-naive patients with progressive metastatic CRPC were randomized to the LEN + DP arm (oral [p.o.] LEN 25 mg/day on days 1–14 of each 21-day cycle) or the PBO + DP arm (PBO in the same schedule). In both arms, docetaxel was administered intravenously at 75 mg/m2 on day 1 of each cycle, and prednisone was dosed 5 mg p.o. twice daily. Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), objective response rate, and safety. Patient enrollment was completed in Nov 2011 with a total of 1059 patients randomized. The data analysis results were based on the cut-off date of Jan. 13, 2012. Results 533 patients were randomized in the LEN + DP and 526 patients in the PBO + DP arm. The arms were well balanced; mean age was 69 years and ECOG PS scores were 0 in 48.1% and 1 in 47.5% of patients. Median number of cycles administered was 6 and 8 in the LEN + DP and PBO + DP arms, respectively. The most common grade ≥ 3 adverse events in the LEN + DP arm included neutropenia (22%), febrile neutropenia (12%), neutropenic sepsis (3%). Vascular events grade > 3 were reported in 7.4% of patients in the LEN + DP arm versus 4.4% in the PBO + DP arm. No increased mortality due to toxicity was seen. Median OS and PFS was 77 and 45 weeks in the LEN + DP arm, compared to median not reached (p = 0.0017) and 46 weeks (p = 0.0187), in the PBO + DP arm, respectively. Hazard ratio (LEN over PBO) is 1.53 (95% CI = 1.17 to 2.00) for OS and 1.32 (95% CI = 1.05 to 1.66) for PFS. Conclusions The addition of LEN to DP did not improve OS in patients with CRPC and was associated with greater toxicity. Shorter treatment duration, lower dose intensity and earlier treatment discontinuation might have contributed to this lack of benefit. Studies to explain the poorer outcome of the LEN arm are underway. Disclosure D.P. Petrylak: Advisory board: Amgen, Bayer, Pfizer, Ferring, Millenium, Novartis, Dendreon, Johnson and Johnson, GlaxoSmithKline. Corporate sponsored research: Celgene, Dendreon, Sanofi, Pfizer, AstraZeneca, GlaxoSmithKline, Rogesen institute, Boehringer Ingelheim. K. Fizazi: Participation to advisory boards for Sanofi-Aventis and Celgene C.N. Sternberg: Honoraria: Johnson + Johnson, Astellas, Amgen and Sanofi-Aventis Research funding: Cougar J. Bellmunt: Consultancy and adboard contribution for Cellgene and Sanofi (compensated) D. Barton: Celgene employee and stock owner A. Fandi: Celgene employee and stock owner U. Jungnelius: Celgene Corporation: Company employee S. Li: Statistician working at Celgene. I have Celgene stock options as a regular employee. N. Vogelzang: Member of the MAINSAIL steering committee, did not receive direct funds from Celgene for conducting the research as it was conducted thru US Oncology/McKesson. Honoraria from Celgene for lectures. Salary compensation from US Oncology Research All other authors have declared no conflicts of interest.