Outcomes in Patients With Metastatic Renal Cell Carcinoma Who Develop Everolimus-Related Hyperglycemia and Hypercholesterolemia: Combined Subgroup Analyses of the RECORD-1 and REACT Trials.

Abstract

BACKGROUND:

Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors. The purpose of this study was to characterize safety and efficacy of patients with metastatic renal cell carcinoma (mRCC) treated with everolimus in RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily) and REACT (RAD001 Expanded Access Clinical Trial in RCC) who developed these events.

PATIENTS AND METHODS:

Adults with vascular endothelial growth factor-refractory mRCC received everolimus 10 mg/d in the randomized RECORD-1 (n = 277) and open-label REACT (n = 1367) studies. Outcomes included safety, treatment duration, overall response, and progression-free survival for patients who developed hypercholesterolemia or hyperglycemia.

RESULTS:

In RECORD-1, 12% (33 of 277) and 20% (55 of 277) of patients developed any grade hyperglycemia or hypercholesterolemia, respectively, with only 6% (78 of 1367) and 1% (14 of 1367) of the same events, respectively, in REACT. Median everolimus treatment duration was similar for patients with hyperglycemia or hypercholesterolemia (RECORD-1, 6.2 and 6.2 months, respectively; REACT, 4.4 and 4.5 months, respectively), but longer than the overall populations (RECORD-1, 4.6 months; REACT, 3.2 months). In RECORD-1/REACT, 82%/68% of patients with hyperglycemia and 75%/71% of patients with hypercholesterolemia achieved partial response or stable disease. The incidence of clinically notable Grade 3 or 4 adverse events, other than anemia and lymphopenia, appeared to be similar across trials and subgroups. Although there was a trend for improved progression-free survival with development of hyperglycemia or hypercholesterolemia, the association was not statistically significant.

CONCLUSION:

Hyperglycemia and hypercholesterolemia were observed in low numbers of patients, and although these events might be associated with improved response to everolimus, the differences were not significant. These findings should be validated with prospective biomarker studies.

• Authors: Petri Bono, Stephane Oudard, Istvan Bodrogi, Thomas E Hutson, Bernard Escudier, Jean-Pascal Machiels, John A Thompson, Robert A Figlin, Alain Ravaud, Mert Basaran, Camillo Porta, Sergio Bracarda, Thomas Brechenmacher, Chinjune Lin, Maurizio Voi, Viktor Grunwald, Robert J Motzer
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 14 Issue 5 Pg. 406-414 (10 2016) ISSN: 1938-0682 [Electronic] United States
• PMID: 27287020 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Everolimus

Topics

• Adult
• Antineoplastic Agents (administration & dosage, adverse effects)
• Carcinoma, Renal Cell (drug therapy)
• Disease-Free Survival
• Drug Administration Schedule
• Everolimus (administration & dosage, adverse effects)
• Female
• Humans
• Hypercholesterolemia (chemically induced, epidemiology)
• Hyperglycemia (chemically induced, epidemiology)
• Kidney Neoplasms (drug therapy)
• Male
• Middle Aged
• Prospective Studies
• Survival Analysis
• Treatment Outcome