Advances in the Treatment of Metastatic Renal Cell Carcinoma

Aaron Nethercott, Mercer University College of Pharmacy

According to the National Comprehensive Cancer Network (NCCN) guidelines for kidney cancer anti-VEGF (vascular endothelia growth factor) therapies are first line treatment for metastatic renal cell carcinoma.  After progression, the next recommended line of therapy is considered to be an anti-VEGFR (vascular endothelia growth factor receptor) medication or everolimus[1].  Lenvatinib is a multi-target anti-VGFR medication currently indicated for metastatic, radioactive iodine-refractory differentiated thyroid cancer [2].

Table 1

  Lenvatinib, Everolimus, and the Combination in Patients with Metastatic Renal Cell Carcinoma: a Randomised, Phase 2, Open-Label, Multicentre trial
Design Randomized phase 2 open-label multicenter trial (N = 153)
Objective To compare the efficacy and safety of the established maximum tolerated dose of the lenvatinib plus everolimus combination and single-agent lenvatinib with the standard dose of single-agent everolimus in patients with metastatic renal cell carcinoma who had disease progression after one previous VEGF-targeted therapy
Study Groups Patients were randomized to receive lenvatinib 24 mg/day (n = 52), everolimus 10 mg/day (n = 50), or lenvatinib 18 mg/day plus everolimus 5 mg/day (n = 51)
Methods Advanced or metastatic renal cell carcinoma patients who had responded to VEGF-targeted therapy were randomized into one of the three study groups.  Radiographic tumor response was assessed every eight weeks.
Duration March 16, 2012 to Dec 10, 2014
Primary Outcome Measure Progression-free survival in the intention-to-treat population
Baseline Characteristics Levatinib plus everolimus Lenvatinib Everolimus
Age (years) 61 (44 – 79) 64 (41 – 79) 59 (33 – 77)
Men (%) 69 75 76
One metastases, n (%) 18 (35%) 9 (17%) 5 (10%)
Two metastases, n (%) 15 (29%) 15 (29%) 15 (30%)
Greater than three metastases, n (%) 18 (35%) 28 (54%) 30 (60%)
Previous nephrectomy, n (%) 44 (86%) 43 (83%) 48 (96%)
Results Levatinib plus everolimus Lenvatinib Everolimus
Progression free survival, months (95% Confidence interval) 14.6 (5.9 – 20.1) 7.4 (5.6 – 10.2) 5.5 (3.5 – 7.1)
Adverse Events Common Adverse Events: decreased appetite (lenvatinib/everolimus 83%, lanvatininb 62%, everolimus 18%), vomiting (envatinib/everolimus 53%, lenavatinib 50%, everolimus 10%), nausea (lenvatinib/everlimus 40%, lenvatinib 62%, everolimus 16%), cough (lenvatinib/rvrtolimus 31%, lenvatinib 17%, Eerolimus 30%)
Serious Adverse Events: Cerebral hemorrhage (3.9% of lenvatinib plus everolimus group), myocardial infarction (2% of lenvatinib group)
Percentage that Discontinued due to Adverse Events: 16%
Study Author Conclusions Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after previous VEGF-targeted therapy.  Further study of lenvatinib is warranted in patients with metastatic renal cell carcinoma.

The study found both lenvatinib plus everolimus and lenvatinib on its own to be effective therapies.  It is worth noting that both of these groups had increased survival when compared with everolimus, a highly recommended treatment by the NCCN guidelines. The smaller progression free time in the everolimus group could also be attributed a larger number of people with greater than three metastases in that study group.   As advances continue to be made in cancers treatment.  Combination of different medications may provide increased outcomes and reduced side effects as advances continue to be made in cancer treatment.


  1. Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 2.2014. J Natl Compr Canc Netw. 2014;12(2):175-82.
  2. Lenvima® (lenvatinib) [Package insert]. Woodcliff lake, NJ. Patheon Inc. 2015
  3. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015.

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