Clinical trial shows the significant therapeutic effect of a combination treatment against advanced kidney cancer


View:195 Time:2018-02-12


Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a natural process essential for healing and reproduction. Normally, the process of angiogenesis is well controlled by a network of chemical signals in the body so that blood vessels form only when and where they are needed. However, cancer can hijack this mechanism to facilitate its growth and spread. Cancer cells grow and divide rapidly, and this requires large amounts of oxygen and nutrients that are delivered by blood vessels. A tumor relies on fast-growing networks of blood vessels to sustain its rapid growth. Therefore, blocking angiogenesis represents a therapeutic strategy for cancer.

Scientists have been trying to developing angiogenesis inhibitors, and some angiogenesis inhibitors have already been used in the clinic. One example is axitinib (Inlyta), which was developed by Pfizer and received approval from US FDA for treatment of renal cell carcinoma (the most common type of kidney cancer in adults) in 2012. Axitinib is a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases 1, 2, and 3.

According to a new study published in the journal Lancet Oncology on 10 February 2018, combining axitinib with an immunotherapy called pembrolizumab (Keytruda) provides better therapeutic effects in patients with advanced kidney disease. In previous studies, scientists tried to combine anti-angiogenesis agents with checkpoint inhibitors (a group of immunotherapy), but these combination treatments were often associated excess toxicity. So, findings of the new study are very exciting. The new study was carried out by researchers from Georgetown-Lombardi Comprehensive Cancer Center, Fox Chase Cancer Center, Vanderbilt University Medical Center, Moffitt Cancer Center, Beth Israel Deaconess Medical Center, New York University Langone Medical Center, Wayne State University, Roswell Park Cancer Institute, Ohio State University Wexner Medical Center, Dana-Farber Cancer Institute, and Pfizer.

The new study enrolled patients with previously untreated advanced renal cell carcinoma. The patients received axitinib plus pembrolizumab. The majority of the patients receiving the combination treatment showed tumor shrinkage, according to the first author of the study, Prof Michael Atkins from Georgetown-Lombardi Comprehensive Cancer Center. The combination of axitinib and pembrolizumab was more effective than the two drugs used alone. Importantly, the combination treatment was well tolerated -- no unexpected toxicities were observed. Collectively, these results reveal that the combination of axitinib and pembrolizumab may improve the treatment of advanced kidney cancer. Moreover, the study may also have implications for treatment of other types of cancer. Further clinical trials will compare the combination therapy tested in this study with other anti-angiogenesis agents.

Checkpoint inhibitors such as pembrolizumab are an important type of immunotherapy. These therapies target immune checkpoint molecules, which are regulators of the immune system and are crucial for self-tolerance. Examples of immune checkpoint molecules include CTLA4 and PD-1 and PD-L1. The drug pembrolizumab is a humanized antibody that targets and blocks PD-1 on certain immune cells. It has been approved to treat metastatic melanoma. Checkpoint inhibitors and other types of immunotherapy have emerged in last decade as a promising therapeutic approach in various diseases. An immunotherapy may be used alone or in combination with conventional treatments. Recent research breakthroughs and clinical successes have brought immunotherapy to the forefront of the medical community.
 
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