Immunotherapy for kidney cancer—also called renal cell cancer—has tremendously changed the treatment landscape and overall survival of patients with metastatic kidney cancer.
The kidneys, located on each side of the body toward the back of the abdominal cavity, filter blood, clear waste, and make urine. A person can live with only one functioning kidney.
About 9 out of every 10 kidney cancers are renal cell carcinomas—cancers that form in the lining of the tubules inside the kidney. About 7 out of 10 people with renal cell carcinoma have a subtype called clear cell carcinoma. Non-clear cell kidney cancers include papillary, chromophobe, mucinous tubular and spindle cell (MTSC), Xp11.2 translocation, medullary, and unclassified.
In its early stages, kidney cancer typically has no symptoms. As a tumor grows, symptoms may include blood in the urine, pain or a lump in the lower back or abdomen, fatigue, weight loss, and swelling in the ankles or legs. Often a tumor will be discovered when a patient has a CT scan or ultrasound for another reason.
Risk factors for kidney cancer include tobacco use, obesity, high blood pressure, chronic renal failure, and exposure to certain industrial chemicals, such as trichloroethylene, or radiation.
Globally, there are an estimated 400,000 cases of kidney cancer diagnosed each year, along with 175,000 deaths. Kidney cancer is the eighth most common malignancy in the United States, and there will be an estimated 76,000 new cases and 14,000 deaths in 2021. If kidney cancer is diagnosed while the cancer is still local (has not spread beyond the kidney), the five-year survival rate is 93 percent. Like most cancers, kidney cancer is difficult to treat once it has spread to other parts of the body. Metastatic kidney cancer has a five-year-survival rate of 12 percent.
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Treatment for kidney cancer depends on individual factors, including the exact location of the tumor, stage of the tumor, and the person’s general health. Treatments for early stages (1-3) kidney cancer include surgery, laproscopy, ablation, and targeted therapy. Patients with advanced or metastatic kidney cancer are treated with systemic therapy that includes targeted therapy and immunotherapy. Kidney cancer tends to be resistant to both chemotherapy and radiation therapy.
Immunotherapy is a type of therapy that takes advantage of a person’s own immune system to help kill cancer cells. The first indication that kidney cancer might be a good target for immunotherapy came from the observation that patients with metastatic kidney cancer occasionally experienced spontaneous regressions after surgical removal of the primary tumor. In the past, immunotherapies in the form of immune-stimulating chemicals called cytokines were a common first-line therapy for advanced kidney cancer, but today are used only for cancers unresponsive to targeted therapies because of the risk of serious side effects. (The cytokines interleukin-2 (IL-2) and interferon-alpha cause kidney cancers to shrink in approximately 10-20 percent of patients and provide durable remissions in a subset of these patients.) Several newer immunotherapies, in particular PD-1/PD-L1 and CTLA-4 checkpoint inhibitors, have become an integral part of the management of advanced or metastatic kidney cancer.
There are currently seven FDA-approved immunotherapy options for kidney cancer either as a single agent or in combination with another immunotherapy or targeted therapy.
- Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced kidney cancer
- Aldesleukin (Proleukin®): a cytokine that targets the IL-2/IL-2R pathway; approved for subsets of patients with advanced kidney cancer
- Avelumab (Bavencio®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced kidney cancer, including as a first-lien therapy in combination with chemotherapy
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced kidney cancer that has DNA mismatch repair deficiency (dMMR)
- Ipilimumab (Yervoy®), a checkpoint inhibitor that targets the CTLA-4 pathway; approved, in combination with nivolumab, for subsets of patients with advanced kidney cancer
- Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced kidney cancer, including as a first-line therapy in combination with chemotherapy
- Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced kidney cancer, including as a first-line therapy
Several ongoing trials are testing the feasibility of using immunotherapy in early-stage kidney cancer, alone and in combination with surgery.
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The Cancer Research Institute has supported the best scientists in the field working toward the improvement of kidney cancer treatment, including funding for research on IL-2 and interferon and newer treatment approaches using checkpoint blockades. CRI also funded a clinical trial of interferon-alpha in human patients in 1978, work that demonstrated kidney cancer's sensitivity to interferon—paving the way for treatment’s approval by the FDA.
- In 1993, based on promising laboratory findings, CRI provided financial support for a phase 1 clinical trial for patients with metastatic renal cell carcinoma, leading to the creation of GVAX, a therapeutic cancer vaccine.
- In 1999, CRI-funded researchers used SEREX technology in identifying tumor-related antigens in patients with renal cell carcinoma, providing a solid foundation for the theory that renal cancer could be immunogenic—recognizable by the human immune system.
- In 2010, several CRI researchers successfully completed a phase 1 study that showed a monoclonal antibody (PD-1 blockade) could induce frequent tumor regressions in renal cancer, among other cancer types, with low toxicity rates.
- In 2012, CRI CLIP Investigator Jeffrey Rathmell, Ph.D., of Vanderbilt University discovered that anti-tumor T cells in kidney cancer were found to be dependent on glucose and fail to function without it.
- In 2015, the CRI Anna-Maria Kellen Clinical Accelerator launched a clinical study that seeks to determine the effectiveness of combining the CTLA-4 inhibitor tremelimumab, with the PD-L1 inhibitor durvalumab, in patients diagnosed with various advanced solid tumors who have failed standard therapy.
Explore CRI's current support for kidney cancer research in our funding directory.
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