But if confirmed, this could represent an important new
direction in our ability to assess the prognostic significance
of such biomarkers.
Conclusion
Evidence from two pivotal trials comparing new therapeutic
approaches as initial therapy for patients with
metastatic RCC of poor or intermediate risk to a long
standing standard of care sunitinib are likely to have a
meaningful impact on the treatment paradigm if one or
both of these options is approved, as expected in early
2018. This may mean that for the first time in more than
10 years, the standard of care in these patients, which has
been sunitinib, will undergo significant change with the
approval of Cabometyx achieved in 2017 and the expected
approval of ipi-nivo in 2018.
References
1. Yakes FM, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and
VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis,
and tumor growth. Mol Cancer Ther. 2011;10:2298-2308.
2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus
in advanced renal-cell carcinoma. N Eng J Med. 2015;373:1814-
1823.N Engl J Med. 2015 Nov 5;373(19):1814-23
3. Park K, Lee J-L, Park I, et al. Comparative efficacy of vascular
endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) and
mammalian target of rapamycin (mTOR) inhibitor as second-line
therapy in patients with metastatic renal cell carcinoma after the failure
of first-line VEGF TKI. Med Oncol. 2012;29:3291-3297.
4. Cabometyx prescribing information revision, December 2017.
100 Kidney Cancer Journal
5. ChoueiriTK, Hessel C, Halabi S, et al. Progression-free survival by
independent review and overall survival update for the Alliance
A031203 CABOSUN trial of cabozantinib vs sunitinib in metastatic renal
cell carcinoma. 2017 ESMO annual meeting, Sept. 8-12, Madrid, Spain;
oral presentation #LBA38.
6. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus
everolimus in advanced renal-cell carcinoma. N Eng Med. 2015;373:
1803-1813.
7. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab
in patients with metastatic melanoma. N Engl J Med. 2010;33:
7711-23.
8. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab + ipilimumab
vs sunitinib for treatment-naïve advanced or metastatic renal cell carcinoma
(RCC): results from CheckMate214, including overall survival by
subgroups. Society for Immunotherapy for Cancer 2017 meeting; Abstract
038.
9. Ko JJ, Choueiri TK, Rini BI, et al: First-, second-, third-line therapy for
mRCC: Benchmarks for trial design from the IMDC. Br J Cancer.
2014;110:1917-1922
10. Stukalin I, Alimohamed N, Heng DY: Contemporary treatment of
metastatic renal cell carcinoma. Oncol Rev. 2016 10:295.
11. Beuselinck B, Oudard S, Rixe O, et al: Negative impact of bone metastasis
on outcome in clear-cell renal cell carcinoma treated with sunitinib.
Ann Oncol. 2011; 22:794-800.
12. Choueiri TK, Escudier B, Powles T, et al: Cabozantinib versus
everolimus in advanced renal cell carcinoma (METEOR): Final results
from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016; 17:917-
927.
13. Gherardi E, Birchmeier W, Birchmeier C, et al. Targeting MET in cancer:
rationale and progress. Nat Rev. Cancer. 2012;12:89-10.
14.Giubellino A, Linehan WM, Bottaro DP. Targeting the MET signaling
pathway in renal cancer. Expert Rev Anticancer Ther. 2009;9:785-793.
15. Rankin EB, Giaccia AJ, The Receptor Tyrosine Kinase AXL in Cancer
Progression. Cancers.2016;88:pii:E103.
16. Zhou L, Liu XD, Sun M, et al. Targeting MET and AXL overcomes resistance
to sunitinib therapy in renal cell carcinoma. Oncogene. 2016;35:
26687-2697. KCJ
Kidney Cancer Journal,
Now in Its 16th Year
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• Highlights and analyses from the 2018 GU ASCO
Meeting, February 8-10, San Francisco.