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.
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.
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.
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.
Clinical genitourinary cancer. 2016 Apr 27 [Epub ahead of print]
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
Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Finland. Electronic address: ., Department of Oncology, Georges Pompidou Hospital, Paris, France., National Institute of Oncology, Budapest, Hungary., Medical Oncology, US Oncology/Baylor-Sammons Cancer Center, Dallas, TX., Immunotherapy Unit, Gustave Roussy Institute, Villejuif, France., Institut Roi Albert II, Service d'Oncologie Médicale, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université catholique de Louvain, Brussels, Belgium., Medical Oncology, Seattle Cancer Care Alliance, Seattle, WA., Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA., Medical Oncology Hôpital, Saint André CHU, Bordeaux, France., Institute of Oncology, Istanbul University, Istanbul, Turkey., Medical Oncology, IRCCS San Matteo University Hospital Foundation, Pavia, Italy., Medical Oncology, San Donato Hospital, Istituto Toscano Tumori (ITT), Arezzo, Italy., Novartis Pharma S.A.S., Rueil-Malmaison, France., Novartis Pharmaceuticals, East Hanover, NJ., Novartis Pharmaceuticals, East Hanover, NJ., Clinic for Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School Hannover, Hannover, Germany., Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY.