Cabozantinib versus everolimus in advanced renal-cell carcinoma Journal Article
| Authors: | Choueiri, T. K.; Escudier, B.; Powles, T.; Mainwaring, P. N.; Rini, B. I.; Donskov, F.; Hammers, H.; Hutson, T. E.; Lee, J. L.; Peltola, K.; Roth, B. J.; Bjarnason, G. A.; Geczi, L.; Keam, B.; Maroto, P.; Heng, D. Y. C.; Schmidinger, M.; Kantoff, P. W.; Borgman-Hagey, A.; Hessel, C.; Scheffold, C.; Schwab, G. M.; Tannir, N. M.; Motzer, R. J. |
| Article Title: | Cabozantinib versus everolimus in advanced renal-cell carcinoma |
| Abstract: | BACKGROUND Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression- free survival. Secondary efficacy end points were overall survival and objective response rate. RESULTS Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. CONCLUSIONS Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. Copyright © 2015 Massachusetts Medical Society. |
| Keywords: | survival; adult; controlled study; aged; aged, 80 and over; disease-free survival; middle aged; survival analysis; major clinical study; overall survival; clinical trial; constipation; fatigue; mortality; sorafenib; bevacizumab; sunitinib; advanced cancer; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; hypophosphatemia; antineoplastic agents; pyridines; alpha interferon; comparative study; disease free survival; antineoplastic agent; interleukin 2; progression free survival; quality of life; anemia; mucosa inflammation; nausea; randomized controlled trial; stomatitis; vomiting; weight reduction; creatinine; creatinine blood level; kidney carcinoma; kidney neoplasms; abdominal pain; arthralgia; asthenia; backache; coughing; dizziness; dyspnea; fever; hyperglycemia; hypomagnesemia; pneumonia; pruritus; rash; alanine aminotransferase; aspartate aminotransferase; hypokalemia; carcinoma, renal cell; multicenter study; drug response; pazopanib; peripheral edema; open study; headache; phase 3 clinical trial; hypothyroidism; axitinib; dyspepsia; hand foot syndrome; muscle spasm; dry skin; epistaxis; everolimus; proteinuria; rapamycin; sirolimus; anilides; aspergillosis; hypertriglyceridemia; leg pain; aspiration pneumonia; dysgeusia; pyridine derivative; anilide; decreased appetite; dysphonia; abnormal laboratory result; hypertransaminasemia; cabozantinib; body weight disorder; arm pain; nivolumab; very elderly; humans; human; male; female; priority journal; article; analogs and derivatives |
| Journal Title: | New England Journal of Medicine |
| Volume: | 373 |
| Issue: | 19 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2015-11-05 |
| Start Page: | 1814 |
| End Page: | 1823 |
| Language: | English |
| DOI: | 10.1056/NEJMoa1510016 |
| PUBMED: | 26406150 |
| PROVIDER: | scopus |
| PMCID: | PMC5024539 |
| DOI/URL: | |
| Notes: | Export Date: 2 December 2015 -- Source: Scopus |
