Immunotherapy innovations beneficial in kidney cancer treatment

While kidney cancer is uncommon in patients younger than age 45, there’s an increasing incidence in diagnosis in young people because of the advent of imaging technology, according to Dr. Nazanin Fallah-Rad, medical oncologist at Princess Margaret Cancer Centre and Mount Sinai Hospital.

“There’s an increasing incidence of younger people being diagnosed with kidney cancer and a lack of access to care — and sometimes, there’s a lack of availability for the drugs needed,” she said during a session at Benefits Canada’s 2020 Employers Cancer Care Summit on Mar. 3.

For patients with localized kidney cancer, the survival rate at five years is 93 per cent, she added, but once the cancer spreads to surrounding structures, known as locally advanced disease, the survival rates go down to 75 per cent. “If a patient presents with advanced disease — metastatic disease that’s gone to different parts of their body — the survival rates go down significantly to 12 per cent.”

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With advanced kidney cancer, morbidity depends heavily on the burden of disease. Three-quarters of patients will present between stages one and three, but a quarter will present with advanced disease, said Dr. Fallah-Rad, noting kidney cancer is unique in that it behaves more erratically and can travel to the lungs, bones, lymph nodes, liver, adrenal glands and brain.

In addition, there’s toxicity that comes from treatment and side-effects can vary from fatigue to high blood pressure to dry skin or sore hands and feet, she noted. The duration of these toxicities can differ depending on the treatment, she added, and a lot of tough problems arise once treatment begins. “Drug toxicities themselves can be a cause for a lot of disability, but we’re finding that by looking at doses or the way we administer a drug, we can work around these toxicities fairly well.”

The nature of how advanced kidney cancer evolves is intricate — as cancer forms in the body, it releases antigens, which cause the immune system to dispatch cells into the blood vessels. From there, the immune cells travel to the cancer site and, ideally, kill it. “There’s a complex network that happens — cross-talk between tumours, the blood vessels that take the cancer to other parts of the body and the immune cells which recognize antigens,” said Dr. Fallah-Rad. “At every point, there’s an opportunity to treat the cancer.”

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With the understanding of how cancer pathways multiply and spread, drugs called tyrosine kinase inhibitors have been developed, she said, noting they work by blocking the tumour’s ability to produce blood vessels. In 2007, TKIs became a standard of care and were used in frontline treatment for patients with advanced kidney cancer. However, they did have limitations as some patients weren’t responding well. “We learned to stratify patients based on their risk and . . . we understood there was an area of unmet need for aggressive forms of kidney cancer where patients were dying very quickly.”

The natural next step came from combining TKIs with immunotherapy. In 2019, two trials looked at immunotherapies plus the pills versus just the pills alone. The result was amazing responses in patients with advanced kidney cancer, said Dr. Fallah-Rad. “The patients who receive the combination are living longer. At the 12-month mark, 89 per cent of patients were alive versus 78 per cent in those only taking the pill.”

Health Canada has since approved the drugs, she said, and oncologists no longer recommend the pill alone for the treatment of advanced kidney cancer; they recommend a combination of immunotherapy plus TKIs.

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However, when it comes to kidney cancer, the duration of treatment isn’t always clear and there’s some debate in the oncology community about how long patients should be kept on an immunotherapy if they’ve had a good response, said Dr. Fallah Rad. “How long do we continue this drug? It’s hard to tell a patient to stop a treatment that’s practically cured them.”

“There’s a profound cost to the public health-care system,” she added. “Many of these treatments are expensive and understanding the implications is important.”

Read more coverage from the 2020 Employers Cancer Care Summit.