Tyrosine kinase inhibitors (TKIs) and immunotherapy drugs — as well as the combination of the two — have moved the needle forward when it comes to kidney cancer outcomes, according to an expert in the space.

However, the side effects from these treatments may be different from the chemotherapy-related toxicities that patients may be more familiar with.

“(TKIs and immunotherapy drugs) work in different ways,” Dr. Jeff Yorio, a medical oncologist at Texas Oncology, said in an interview with CURE®. “Hopefully the side effects are not quite what you see with chemotherapy, but of course, they do come with side effects.”

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Yorio explained that immunotherapy agents, such as Opdivo (nivolumab) and Yervoy (ipilimumab), which are both approved in the kidney cancer setting, work by blocking certain molecules on cancer cells that help them hide from the immune system. In doing so, the drugs lead to an activation — and potential overstimulation — of the immune system.

As a result, a patient’s immune system can end up attacking or causing inflammation in any organ. Commonly, patients experience pneumonitis (inflammation of the lung) or colitis (inflammation of the gastrointestinal tract), which can cause severe diarrhea. Immunotherapy can also affect the thyroid, resulting in hypothyroidism, which may result in a slowing down of the metabolism and weight gain.

“Not everybody gets those effects. Some people cruise through, and have very little side effects, and others can get these much more severe immune effects,” Yorio said. “So they’re certainly not totally benign drugs.”

Similar to immunotherapy agents, TKIs work by blocking something on cancer cells that result in cell death. In this instance, TKI drugs inhibit enzymes that are crucial in the growth of cancer.

“Some of the things that we’re targeting with TKIs do exist in normal cells, so that’s where a lot of the side effects can come from,” Yorio said, noting that common side effects include diarrhea, and a difficulty healing if skin gets injured, as well as blistering.

Despite the side effects associated with immunotherapy and TKI treatment, Yorio noted that these treatments are typically still better tolerated than the limited options that were available years ago.

“Twenty years ago, we had very little treatments that were effective in kidney cancer. There was an older immunotherapy called interleukin 2 that started to be used in the 1990s. That was pretty toxic, and not effective for most people,” Yorio said. “Now you have TKIs, you have immunotherapy — two different paths to go down — that we didn’t have years ago … that’s drastically changed outcomes and survival.”

Looking ahead, Yorio noted that he hopes to see immunotherapy and TKI therapy “get smarter” as time goes on.

“I think we’ll hopefully be able to … find better, more effective ways to use the immune system against cancers, hopefully in ways that cause less side effects,” he said. “The same with TKIs. Hopefully as time goes on, you get smarter TKIs that hone in on the right (targets) and leave (healthy cells) alone.”

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