LBA24 - A Phase 3 Study to Evaluate the Efficacy and Safety of Docetaxel and Prednisone (DP) With or Without Lenalidomide (LEN) in Patients with Castrate-Re...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate I
Topics Anticancer agents
Prostate Cancer
Therapy
Biological therapy
Presenter Daniel Petrylak
Authors D.P. Petrylak1, C.N. Sternberg2, N. Budnik3, R. De Wit4, P.J. Wiechno5, J. Bellmunt6, D. Barton7, A. Fandi8, U. Jungnelius7, S. Li9, N. Vogelzang10
  • 1Medical Oncology, Columbia University Medical Center, 10032 - New York/US
  • 2Department Of Medical Oncology, San Camillo and Forlanini Hospitals, Rome/IT
  • 3Clinical Hospital Of Oao Russian Railways, NSHI Dorozhnaya, Rostov-on-Don/RU
  • 4Department Of Medical Oncology, Erasmus Medisch Centrum, Rotterdam/NL
  • 5Department Of Uro-onocology, Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie, Warsaw/PL
  • 6Oncology Department, Hospital del Mar, Barcelona/ES
  • 7Oncology, Solid Tumors, Celgene Corporation, Basking Ridge/US
  • 8Oncology Clinical Research And Development, Celgene Corporation, Basking Ridge/US
  • 9Statistics, Celgene Corporation, Basking Ridge/US
  • 10Oncology Department, US Oncology Research Houston TX and Comprehensive Cancer Centers of Nevada, Las Vegas/US

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-naïve 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.