Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma.
OBJECTIVE
To evaluate the efficacy and toxicity of the combination of bevacizumab, an angiogenesis inhibitor, and everolimus, an mTOR inhibitor, in the treatment of patients with advanced clear cell renal carcinoma.


METHODS
Two groups of patients with metastatic renal cell carcinoma were eligible for this study: those with no previous treatment with targeted agents and those with previous treatment with sunitinib and/or sorafenib. All patients received bevacizumab 10 mg/kg intravenously every 2 weeks and everolimus 10 mg orally daily. Patients were evaluated for response after 8 weeks of treatment; patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred.


RESULTS
Eighty patients (50 untreated, 30 previously treated) entered this clinical trial. The combination of bevacizumab/everolimus showed activity in both groups. Median progression-free survivals in previously untreated and previously treated patients were 9.1 and 7.1 months, respectively. Overall response rates (30% and 23%) were similar in both groups. The regimen was well tolerated by most patients, with a toxicity profile as expected based on the known toxicities of these two agents. Grade 3 to 4 proteinuria was more frequent than expected (25%) and led to treatment discontinuation in six patients.


CONCLUSIONS
Bevacizumab/everolimus is active and well tolerated in the treatment of advanced clear cell renal cancer, either as first-line treatment or after treatment with sunitinib and/or sorafenib. The benefits of this combination regimen, versus sequential use of these two agents, requires further study.
Hainsworth
John D
JD
Sarah Cannon Research Institute, 3322 West End Ave, Suite 900, Nashville, TN 37203, USA. jhainsworth@tnonc.com
Spigel
David R
DR
Burris
Howard A
HA
Waterhouse
David
D
Clark
Bobby L
BL
Whorf
Robert
R
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D000068258:Bevacizumab; D000068338:Everolimus; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus