Kidney Cancer Awareness Month: Renal Cell Carcinoma & Immunotherapy
March is Kidney Cancer Awareness Month in the United States. This is a good time to learn more about kidney cancer and its risk factors, detection, and treatment.
Kidney cancer occurs when there is abnormal growth of cells in the kidneys. The most common type of kidney cancer is renal cell carcinoma, accounting for 90 percent of kidney cancer cases. Risk factors for developing kidney cancer include smoking, obesity, high blood pressure, and occupational exposures to certain dyes, solvents, and asbestos.
About 76,000 cases of kidney cancer will be diagnosed in the United States in 2021, and nearly 14,000 people will die from kidney cancer. Most of those diagnosed with kidney cancer are older. Men are twice as likely to develop kidney cancer than women. Kidney cancer is more common in African American and American Indian/Alaskan Native populations.
Kidney cancer is often only detected by chance during other imaging procedures. If detected early enough and the cancer hasn’t spread, kidney cancer can often be treated through surgery alone. Advanced kidney cancer is typically treated by immunotherapy and other targeted therapies.
Immunotherapy is a type of cancer treatment that uses the body’s immune system to prevent, control, and eliminate cancer. Immunotherapy can train the immune system to recognize and attack cancer cells. It also can boost immune cells to help them eradicate cancer cells. Immunotherapy comes in a variety of forms, several of which are used to treat kidney cancer. All forms of immunotherapy are the direct result of clinical trials.
Research into immunotherapy and kidney cancer began in the 1980s. Researchers were well aware that kidney cancer was a particularly immunologically active cancer. Kidney cancer cells are able to suppress the immune system. Research hypothesized that if they could find a way to harness the immune system to fight against the kidney cancer cells they may be able to slow the growth or fight against kidney cancer cells.
In 1985, a study examined an immunotherapy treatment called Interleukin 2 (IL-2) on 149 patients with metastatic renal cell carcinoma. Metastatic means the cancer that began in the kidneys has spread to other parts of the body. IL-2 is one type of immunotherapy in a group called cytokines. Cytokines are small proteins that boost the immune system.
20 percent of patients responded to IL-2 and experienced long-term tumor shrinkage. The Food & Drug Administration (FDA) approved IL-2 to treat renal cell carcinoma in 1992, and it became the standard therapy. Another type of cytokine therapy called interferon was also developed during this time.
While IL-2 and interferon were successful in treating and even curing cancer in some individuals, the success rate was still low at 20 percent or lower and it caused serious side effects, so researchers hoped to find a more effective therapy. Researchers also developed different types of targeted therapies, including chemotherapy, to treat kidney cancer in combination with immunotherapy at this time.
Other drugs were developed to treat kidney cancer throughout the 2000s, but great success was found with clinical trials on a type of immunotherapy called immune checkpoint inhibitors. The immune system uses proteins on immune cells, referred to as checkpoints, to turn an immune response on or off. This keeps the immune system from attacking normal cells. Kidney cancer can use these checkpoints to avoid being fought off by the body’s immune system. Immune checkpoint inhibitors target the protein checkpoints to restore the body’s immune response against kidney cancer cells and attack them.
In 2015, a study examined whether nivolumab, a PD-1 (a specific type of protein checkpoint) inhibitor, could extend survival for patients with renal cell carcinoma, compared to standard treatment at the time called everolimus. 821 patients were randomly assigned to receive either nivolumab or everolimus. Patients who received nivolumab lived about 5 months longer than patients who received everolimus. Patients who received nivolumab also reported significantly fewer adverse events and side effects.
The FDA approved nivolumab as a treatment for advanced renal cell carcinoma in 2015, under the brand name Opdivo. In 2018, studies also looked at combining Opdivo with another type of immunotherapy called Ipilimumab (brand name Yervoy). Yervoy is a CTL-4 (a specific type of protein on T cells) inhibitor. Opdivo and Yervoy are both checkpoint inhibitors and work in different but complementary ways.
1,096 patients with previously untreated renal cell carcinoma received either a combination therapy of Opdivo and Yervoy or another standard therapy called sunitinib. Patients who received the combination therapy lived longer and responded better than patients receiving the standard therapy. As a result, the FDA approved a combination immunotherapy regimen with Opdivo and Yervoy in 2018. More combination immunotherapy regimens were approved in 2019 as well.
Further studies continue to examine whether other types of immunotherapy and other targeted therapies will extend survival and treat kidney cancer. Immunotherapy is a promising treatment for many other cancers as well. Immunotherapy for kidney cancer is a great example of how clinical trials are influential in finding new treatments, applying research to other cancers and diseases, and - most importantly - saving lives.