Addition of Lenalidomide to Docetaxel-Prednisone Worsens Survival in Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer
In the phase III MAINSAIL trial reported in The Lancet Oncology, Petrylak et al found that the addition of lenalidomide (Revlimid) to docetaxel-prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer was associated with significantly worse overall survival. The trial was closed early due to futility.
Study Details
In this double-blind trial, 1,059 patients with progressive disease from 223 centers in Europe, United States, Russia, Australia, South Africa, Israel, Mexico, and Canada were randomly assigned between November 2009 and November 2011 to receive docetaxel 75 mg/m² on day 1 and prednisone 5 mg twice daily on days 1 to 21 and either lenalidomide 25 mg (n = 533) or placebo (n = 526) once daily on days 1 to 14 of each 21-day treatment cycle. The primary endpoint was overall survival in the intention-to-treat population.
The lenalidomide and placebo groups were generally balanced for age (median 70 years in both), region (North America for 26% in both, Europe and Australia for 62% and 63%), type of disease progression (prostate-specific antigen [PSA] only in 30% and 28%, radiographic in 70% and 72%), metastatic sites (bone only in 32% and 30%, soft tissue in 20% and 18%, both in 49% and 52%), median PSA level (105 and 85 ng/mL), and median circulating tumor cell count (5 vs 11).
Worse Overall Survival
At data cutoff in January 2012, after a median follow-up of 8 months, median overall survival was 17.7 months (95% confidence interval [CI] = 14.8–18.8 months) in the lenalidomide group vs not reached in the placebo group (hazard ratio [HR] = 1.53, P = .0017). Overall survival at 1 year was 71.4% vs 78.2%. Death during treatment or at < 28 days since the last dose occurred in 3% vs 2% of patients, and death at > 28 days since last dose, mainly due to disease progression, occurred in 21% vs 15%.
Median progression-free survival was 10.4 vs 10.6 months (HR = 1.32, P = .0187), and progression-free survival at 1 year was 33.8% vs 45.3%. Objective response was observed in 23% vs 25% (odds ratio = 0.884, P = .3975). PSA reduction of ≥ 50% from baseline occurred in 59% vs 58%.
Adverse Events
Adverse events of grade ≥ 3 occurred in 73% of the lenalidomide group vs 58% of the placebo group. Grade 3 or 4 neutropenia (22% vs 16%), febrile neutropenia (12% vs 4%), diarrhea (7% vs 2%), pulmonary embolism (6% vs 1%), asthenia (5% vs 3%), pneumonia (5% vs 1%), and dyspnea (4% vs 2%) were more common in the lenalidomide group.
The investigators concluded: “Overall survival with the combination of lenalidomide, docetaxel, and prednisone was significantly worse than with docetaxel and prednisone for chemotherapy-naive men with metastatic castration-resistant prostate cancer. Further research with this treatment combination is not warranted.”
Daniel P. Petrylak, MD, of Yale Cancer Center, is the corresponding author of The Lancet Oncology article.
The study was funded by Celgene Corporation. For full disclosures of the study authors, visit www.thelancet.com.
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