• Reproductive Cancers
• Oncology Clinical Trials

Lenalidomide, has been used to treat myeloma and myelodysplastic syndrome. When used in combination with docetaxel and prednisone, or as a single agent, it has been shown to demonstrate activity and tolerability in patients with castrate-resistant prostate cancer (CRPC) [Petrylak DP et al. J Clin Oncol 2009]. Daniel P. Petrylak, MD, Yale Cancer Center, New Haven, Connecticut, USA, reported results from the Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination with Docetaxel and Prednisone for Patients with Castrate-Resistant Prostate Cancer [MAINSAIL; NCT00988208] trial, which showed that the addition of lenalidomide to docetaxel and prednisone did not improve overall survival (OS) in CRPC patients and its use was associated with greater toxicity.

This Phase 3, multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of docetaxel plus prednisone as first-line treatment for CRPC. Chemotherapy-naïve patients with progressive metastatic CRPC (effective castration defined as serum testosterone levels <50 ng/dL) and an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ≥2 were randomized to either lenalidomide (25 mg on Days 1 to 14) plus docetaxel (75 mg/m² on Day 1 of each cycle) plus prednisone (5 mg BID on Days 1 to 21) or placebo plus docetaxel plus prednisone at similar doses and scheduling. Treatment phase was 21-day cycles until disease progression. Follow-up for survival occurred every 90 days for up to 5 years following study treatment discontinuation. The primary study endpoint was OS. Secondary endpoints included progression-free survival (PFS), objective response, and safety. Patient enrollment was completed in November 2011, with a total of 1059 patients. The data analysis results were based on the cutoff date of January 13, 2012.

The lenalidomide (n=533) and placebo (n=526) arms were well balanced; mean age was 69 years, and ECOG PS scores were 0 in 48.1% and ≥1 in 51.8% of patients. About 71% of patients had radiographic disease progression. Metastatic sites included bone, soft tissue, and both bone and soft tissue. Median OS and PFS were 77 and 45 weeks in the lenalidomide arm, compared with median not reached (HR, 1.53; 95% CI, 1.17 to 2.00; p=0.0017) and 46 weeks (HR, 1.32; 95% CI, 1.05 to 1.66; p=0.0187; in the placebo arm, respectively. Objective response rate was 22.1 % for lenalidomide versus 24.3% for the placebo arm (p=0.3975). The median number of cycles administered were 6 and 8 in the lenalidomide and placebo arms, respectively. All dose reductions were due to adverse events, except for 2 dose reductions of docetaxel that were due to other reasons.

The most common grade ≥3 adverse events that occurred significantly more often in the lenalidomide group included neutropenia (22%), febrile neutropenia (12%), diarrhea (7%), and pulmonary embolism (6.5%). Significantly more deaths (>28 days from last lenalidomide dose) occurred in the lenalidomide arm (20.8%) compared with the placebo arm (15.0%; p=0.016).

The addition of lenalidomide to docetaxel plus prednisone did not improve OS in patients with CRPC and was associated with greater toxicity. Shorter treatment duration, earlier treatment discontinuation, and lower dose intensity of docetaxel might have contributed to this lack of benefit. Studies to explain the poorer outcome of the lenalidomide arm are under way.

• © 2012 MD Conference Express®