|
Sub-category:
Kidney Cancer
Category:
Genitourinary Cancer
Meeting:
2008 ASCO Annual Meeting
Session Type and Session Title:
null, General Session II: Genitourinary Cancers
Oral Presentation, Genitourinary Cancer (Testes, Kidney, and Bladder)
Abstract No:
LBA5026
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr LBA5026)
Author(s):
R. J. Motzer, B. Escudier, S. Oudard, C. Porta, T. E. Hutson, S. Bracarda, N. Hollaender, G. Urbanowitz, A. Kay, A. Ravaud
Abstract:
Background: RAD001 (everolimus) is an oral inhibitor of mTOR, an intracellular kinase that regulates cell proliferation and angiogenesis. Antitumor activity has been shown in a single-arm Phase-II trial in pretreated mRCC with continuous daily therapy (JCO 2007;25[18S]:261s Abs 5107).
Methods: Pts with RCC with a clear-cell component progressing on or <6 months (mo) after VEGFr-TKI therapy (sorafenib, sunitinib, or both) were randomized 2:1 to RAD001 (10 mg/d po) or placebo, both with best supportive care. Patients were stratified by MSKCC risk criteria and prior VEGFr-TKI therapy (1 vs 2). Progression-free survival (PFS), documented using RECIST and assessed via blinded, independent review, was the primary endpoint. At progression, treatment was unblinded and pts on placebo offered open-label RAD001. Based on a sample size of 362 pts, the trial had 90% power to detect a 33% risk reduction (HR 0.67), with a median exponential PFS improvement from 3.0 to 4.5 mo (stratified log-rank test). Results of a planned interim analysis are presented - as these met prespecified criteria for a positive trial, the Independent Data Monitoring Committee stopped the study to allow remaining patients on placebo to receive RAD001.
Results: From 9/06-10/07, 272 pts were randomized to RAD001 and 138 to placebo. Demographics were well balanced (pooled median age 60y) as was prior VEGFr-TKI therapy (sunitinib 71%, sorafenib 55%, sunitinib+sorafenib 26%). 191 PFS events (47% of 410 pts) were reported by central review: 101 (37%) and 90 pts (65%) on RAD001 and placebo, respectively.
Most common AEs (all grades/grade 3-4) were stomatitis (RAD001 36/4%, placebo 7/0%), anemia (28/7% vs 15/5%), and asthenia (28/2% vs 20/4%). 10% of pts had AEs leading to discontinuation with RAD001 vs 4% with placebo whereas dose reductions were required by 4% vs <1%. 68 deaths were observed, and study follow-up is ongoing to assess the secondary endpoint of overall survival.
Conclusion: RAD001 resulted in a statistically and clinically significant improvement in PFS over placebo with a favorable safety profile in pts with mRCC after progression on other targeted therapies. | Population | N | HR (95% CI) | p-value | RAD001 | Placebo | | | | | | Median PFS (mo) (95% CI) | | All (independent review) | 410 | 0.30 (0.22-0.40) | <0.0001 | 4.0 (3.7-5.5) | 1.9 (1.8-1.9) | All (investigator
review) | 410 | 0.31 (0.24-0.41) | <0.0001 | 4.6 (3.9-5.5) | 1.8 (1.8-1.9) | | Prognostic group: MSKCC risk (independent review) | | Favorable | 118 | 0.35 (0.20-0.61) | <0.0001 | 5.5 (3.8-5.9) | 2.2 (1.9-3.5) | | Intermediate | 231 | 0.25 (0.16-0.37) | <0.0001 | 3.9 (3.5-5.5) | 1.8 (1.8-1.9) | | Poor | 61 | 0.39 (0.19-0.81) | 0.009 | 3.6 (1.9-5.4) | 1.9 (1.7-3.6) |
Abstract Disclosures
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy
and are designated with a caret symbol (^) here and in the print version.
 Associated Presentation(s):
Other Abstracts in this Sub-Category:
Abstracts by R. J. Motzer:
Presentations by R. J. Motzer:
Educational Book Manuscripts by R. J. Motzer:
|
