by Dr. C.H. Weaver M.D. 3/2019
It is estimated there will be 73,820 individuals diagnosed with kidney cancer this year and 14,770 will succumb to their disease. (1) Metastatic renal cell cancer currently has a 5-year survival rate of ~ 12% but several recently approved medications are improving the outcomes for individuals with advanced renal cell cancer. In fact several new medication have been approved or are about to be and the treatment options for renal cell cancer are the best they have ever been.c
Tyrosine Kinase - Checkpoint Inhibitor Immunotherapy Combinations Improve Survival in Advanced Kidney Cancer
Should be the New Standard of Care: Checkpoint inhibitors are novel precision cancer immunotherapy drugs that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD -L1 are the proteins that inhibit this immune response, allowing cancer cells to evade an attack by the body’s immune cells. Checkpoint inhibitor drugs block the PD-1 pathway and enhance the ability of the immune system to fight the cancer.
The US Food and Drug Administration (FDA) has already approved the checkpoint inhibitor Opdivo (nivolumab) combined with Yervoy as first-line, treatment for patients with advanced kidney cancer.
Results from clinical trials evaluating two other checkpoint inhibitor drugs combined with the tyrosine kinase inhibitor Inlyta® (axitinib) are currently being reviewed by the FDA and should be approved shortly and become the new standard of care because these combinations delay cancer recurrence and prolong survival.
Other Medications FDA Approved for the Treatment of Kidney Cancer
Sutent (sunitinib) is an oral targeted agent that works by inhibiting multiple biologic pathways involved in the growth, replication, and spread of cancer cells. Sutent deprives cancer cells of blood and nutrients needed for growth. FDA approved in 2006 and approved in 2017 for use as adjuvant therapy.
Opdivo (nivolumab) is a precision cancer medicine that belongs to a class of medicines called PD-1 inhibitors which help the immune system recognize and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Opdivo works by blocking PD-1, allowing the immune system to work more effectively. FDA approved 2015.
Cabometyx (cabozantinib) is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as other biologic pathways involved in the spread of kidney cancer. Cabometyx is thought to inhibit the action of the receptor tyrosine kinases including MET, VEGFR-1, -2, and -3, AXL, RET, ROS1, TYRO3, MER, KIT, TRKB, FLT-3, and TIE-2. FDA approved in 2016.
Votrient® (pazopanib) is an oral targeted agent that work by inhibiting multiple biologic pathways involved in cancer growth and spread and inhibits angiogenesis which may help slow or prevent the growth of new blood vessels, which deprives the cancer of the oxygen and nutrients it needs to grow.
Inlyta® (axitinib) is an oral targeted drug known as a small-molecule tyrosine kinase inhibitor. It works by blocking certain proteins that play a role in cancer growth. In the US, Inlyta is approved for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. FDA approved in 2012.
Avastin (bevacizumab) is a monoclonal antibody, or protein made in the laboratory, that selectively binds to VEGF. This renders VEGF unable to bind to its receptor on existing vessels and thus halts angiogenesis mediated through this mechanism. Vascular endothelial growth factor (VEGF) is a small protein that promotes angiogenesis. Angiogenesis is the formation of new blood vessels and is a process that is essential for the growth and spread of cancer. Cancer cells need oxygen and nutrients provided by blood in order to grow. The blood vessels formed by angiogenesis supply these necessary nutrients, stimulating cancer cells to replicate and spread. VEGF binds to existing vessels and stimulates them to branch out, ultimately allowing the cancer cells to spread. Many cancer cells have high levels of VEGF and are thought to produce an overabundance of the proteins. FDA approved in 2009.
Lenvima (lenvatinib) is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvima™ also inhibits other RTKs that have been implicated in cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFR?), KIT, and RET. FDA approval in2016.
- National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal pelvis. Available from: . Accessed July 2018.
- Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.
- American Cancer Society. What is kidney cancer? Available from: . Accessed July 2018.
- Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol. 2014; 25(Suppl3):iii49-iii56.
- World Cancer Research Fund International: Kidney cancer statistics. Available from: . Accessed July 2018.