What’s the Deal With Combination Therapy for Kidney Cancer?

by Lara DeSanto Health Writer

Kidney cancer is one of the top 10 most common cancer diagnoses, according to the American Society of Clinical Oncology (ASCO)—and thankfully, big progress has been made in treating it in recent years. In fact, researchers have found that different combinations of newer treatments called immunotherapies and other targeted drugs can help extend the lives of people living with advanced kidney cancer. Learn more about these combination therapies, from how they work to fight cancer growth to side effects to expect.

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Recent Research Breakthroughs Are Game Changers

“The first breakthrough came when we discovered that the driver for the majority of kidney cancers is a broken gene,” says Yasser Ged, M.B.B.S, a medical oncologist at Hopkins Medicine in Baltimore, MD. “Then we developed targeted therapies in the form of pills that target this specific broken gene.” Researchers made another leap forward by developing a new immunotherapy called immune checkpoint inhibitors. “These led to remarkable improvements in how we treat cancer overall,” he says.

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Harnessing the Power of Immunotherapy

All combination therapies include at least one type of immunotherapy—drugs that use the body’s own immune system to attack the cancer. “Immunotherapy blocks a target on the cancer cell that prevents the immune system from seeing it, allowing the immune system uses all of its machinery to try to destroy the cancer cell,” explains Robert Figlin, M.D., a kidney oncologist and deputy director of Cedars-Sinai Cancer in Los Angeles, CA. When an immunotherapy drug is combined with another drug, the two work together to attack the cancer, says Dr. Ged.

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Understanding Targeted Therapy

Other combination therapies pair an immunotherapy drug with a targeted therapy drug called Inlyta (axitinib). Targeted therapies for advanced kidney cancer focus on blocking a specific gene or protein that leads to cancer growth, according to ASCO. Inlyta specifically blocks a protein called vascular endothelial growth factor (VEGF); in most kidney cancers, a mutated gene causes the production of too much VEGF, which increases growth of blood vessels that feed the cancer. Blocking VEGF with this targeted drug helps stop tumor growth.

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3 Therapy Combos to Know

Researchers have found that combining immunotherapies and targeted therapies could improve outcomes for kidney cancer patients even further, says Dr. Ged, compared with using just one drug on its own. The U.S. Food and Drug Administration (FDA) has approved three different combinations for advanced kidney cancer treatment: One combines two immunotherapy drugs called Opdivo (nivolumab) and Yervoy (ipilimumab) and two combine an immunotherapy—either Keytruda (pembrolizumab) or Bavencio (avelumab)—with targeted therapy drug Inlyta.

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Combo Treatments Work for Advanced Kidney Cancer

While treatment of earlier-stage kidney cancers may use individual immunotherapy or targeted therapies, combination therapies are only approved for advanced kidney cancers—and all three combinations have been shown to be effective. “These treatments are currently the best treatments for patients with stage 4 kidney cancer, specifically the subtype clear cell carcinoma, which is the most common type of kidney cancer,” says Dr. Ged. These approaches are also being tested in other kidney cancer scenarios.

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Combination Therapies Help Extend Lives

Compared with other kidney cancer treatment options, combination therapies have shown better outcomes for advanced kidney cancer patients in clinical trials. “They have demonstrated improvements in response rate, progression-free survival, and overall survival compared with single-agent therapies,” says Dr. Figlin. For example, a study found that Opdivo plus Yervoy resulted in people with advanced kidney cancer with poor prognosis living longer with more tumor shrinkage than people who only received one targeted drug, according to the National Cancer Society.

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Combination Therapy Has Side Effects

As with any medical treatment, combination therapies have possible drawbacks. “Side effects can vary from person to person,” says Dr. Figlin. The good news is they are usually easily managed and not severe. Because the three possible treatment combinations show similar efficacy, it can be hard for doctors to know which drug pairing to use for which patient, says Dr. Ged. But since different combos have different side-effect potential—this can help your doctor make the best selection, based on your unique risk factors.

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What to Know About Targeted Therapy Side Effects

So what side effects might you expect if your treatment includes a targeted therapy? “For [targeted] pills, we know the more pills patients take over a longer period of time, the more these drugs build up in the system,” explains Dr. Ged. “Side effects can include fatigue, mouth sores, skin rash, diarrhea, and could increase blood pressure. But on the other hand, once we halt the pills, most of side effects resolve quickly on their own because they wash out from the patient system.”

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Immunotherapy Side Effects Can Be Unpredictable

With immunotherapies, it’s harder to predict which side effects might affect you personally, says Dr. Ged. Remember: Immunotherapy activates the immune system to fight cancer. “Sometimes, when the immune system becomes active, it might misidentify normal tissue and work against that tissue,” explains Dr. Ged. Resulting autoimmune side effects—mainly inflammation—can range from mild to severe, but most are mild, and may affect the lungs, gastrointestinal (GI) tract, liver, or thyroid.

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Treatment Duration May Vary

Based on current recommendations, those taking two immunotherapy drugs should stay on the regimen as long as the cancer is not progressing and side effects are managed, says Dr. Ged. If you’re taking an immunotherapy plus targeted pill combo, the immunotherapy should be taken for no more than two years, but you can continue the targeted pill as long as you can tolerate it and the cancer isn’t progressing. In about 5% to 9% of cases, the cancer may disappear on combination therapy, in which case treatment can be stopped.

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Your Treatment Team Matters

In part due to the risk of side effects of combination therapy for advanced kidney cancer, it’s especially important to seek treatment from a health care team with experience using these therapies. “Patients should recognize that the provider giving the therapy and their team has to be extremely skilled in both managing the treatment and the potential side effects, and oftentimes unskilled providers don’t offer the patients the optimal outcome,” says Dr. Figlin.

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The Bottom Line

Combination therapies are an important breakthrough in kidney cancer treatment, helping patients with advanced forms of this disease to extend their lives. “Most patients want control of their cancer and have opportunities to maintain their quality of life,” says Dr. Figlin, and combination treatments offer these possibilities for a cancer that used to be much more difficult to treat. “When we compare to 10 years ago, we have many more good treatment options that are available,” says Dr. Ged. “Now, we have a multitude of combinations that are quite effective.”

Lara DeSanto
Meet Our Writer
Lara DeSanto

Lara is a former digital editor for HealthCentral, covering Sexual Health, Digestive Health, Head and Neck Cancer, and Gynecologic Cancers. She continues to contribute to HealthCentral while she works towards her masters in marriage and family therapy and art therapy. In a past life, she worked as the patient education editor at the American College of OB-GYNs and as a news writer/editor at WTOP.com.