Here, genitourinary medical oncologist Robert Motzer from Memorial Sloan Kettering Cancer Center (MSK) discusses the latest findings about which patients can benefit most from immunotherapy. Dr. Motzer has helped pioneer treatments for renal cell carcinoma (RCC), the most common type of kidney cancer, as well as other, more rare types.
When is immunotherapy used to treat kidney cancer?
For certain people with advanced or metastatic disease, there’s been a dramatic shift over the past several years toward using immunotherapy drugs called checkpoint inhibitors as a first-line treatment — at the time when patients are initially diagnosed, rather than waiting until after trying chemotherapy, radiation, and surgery.
In 2018, I led a clinical trial that found the combination of two immunotherapies — ipilimumab (Yervoy®) and nivolumab (Opdivo®) — could lead to better outcomes than with the targeted drug sunitinib (Sutent®). At that time, sunitinib was the standard of care for patients who had just been diagnosed with RCC. Based on that study, the U.S. Food and Drug Administration (FDA) approved the ipi/nivo combination for people with advanced RCC whose cancer was found to be at intermediate or high risk of progressing while taking sunitinib.
Since that time, I co-led a clinical trial that showed that nivolumab combined with cabozantinib (Cabometyx®), a targeted drug of the same class as sunitinib, led to a better outcome compared with sunitinib. This combination was approved by the FDA for patients with advanced RCC.
Another immunotherapy drug, pembrolizumab (Keytruda®), has also been approved in combination with other targeted drugs as a first-line treatment for patients who are newly diagnosed with advanced intermediate- or high-risk RCC.
Is combining immunotherapy with other treatments effective against kidney cancer?
There is new, preliminary evidence that adding a targeted therapy to ipi/nivo combination immunotherapy helps some patients. At the recent European Society for Medical Oncology (ESMO) meeting, I was part of a team that presented results from a phase 3 trial that looked at whether adding cabozantinib to ipi/nivo in patients with advanced intermediate- or high-risk kidney cancer could increase the time it took for patients’ cancer to progress (called progression-free survival).
This trial was the first to compare the combination of ipi/nivo alone with giving a triplet combination of ipi/nivo plus cabozantinib for kidney cancer. It included more than 850 patients who were treated at hospitals all over the world. We found that 43% of patients’ cancers responded to the newer combination, compared with 36% to immunotherapy alone. The progression-free survival was longer for the patients who also got targeted therapy compared with those who only got immunotherapy. We plan to continue studying the patients in this trial to find out whether the addition of cabozantinib helps them to live longer.
One downside we found is that that this combination increases the side effects patients experienced. This treatment won’t be right for everyone, and more research is needed to determine who is most likely to benefit from this combination and how it should be given.
How are patients with early-stage kidney cancer treated?
For many patients with disease that has not yet spread beyond the kidney, surgery is often all that’s needed to provide a cure. Surgery may involve removing the entire kidney or just part of it. Surgeons at MSK, led by urologic surgeon Paul Russo, have been at the forefront of developing the best techniques for treating these patients.
Unfortunately, though, some patients with early-stage disease are at significant risk of having their tumors come back and spread after surgery. We use a staging system that looks at the extent of the tumor to predict which patients are at higher risk. Pathologists can also identify tumors that are likely to come back by analyzing the tumor tissue as well as the genes that may be driving the cancer.
Can patients with early-stage kidney cancer benefit from immunotherapy?
Yes. In November 2021, the FDA approved pembrolizumab for patients who have had surgery and whose disease is considered at high risk of coming back. When drugs are given after surgery, we call this “adjuvant” treatment, to reduce the risk of recurrence. Pembrolizumab was the first drug shown to benefit patients with kidney cancer when given after surgery.
At the recent ESMO meeting, we also presented a study that looked at whether patients with early-stage, high-risk disease could benefit from ipi/nivo given as an adjuvant treatment. This multicenter phase 3 clinical trial included more than 800 patients who were randomized to receive either immunotherapy or a placebo. Unfortunately, that trial did not find any benefit for patients. In addition, the patients who received immunotherapy had a lot of side effects.
We are continuing to study this combination, to figure out whether there may be other ways to offer it. We are also focusing on the search for other adjuvant therapies for RCC. The need for additional treatment options for these patients is obviously very great.
Why should people with kidney cancer come to MSK for treatment?
We have led the clinical trials for many of the new drugs that have been approved for kidney cancer over the past 15 years, including both targeted therapies and immunotherapies. We are always focused on providing the most current treatments for our patients, whether that means offering a clinical trial or providing the standard of care.
We also have specialists who can help patients cope with all the side effects of kidney cancer and its treatment. Immunotherapy, especially the ipi/nivo combination, can have a lot of side effects, including damage to the thyroid. Because we developed this drug combination, we have a great deal of experience helping to manage and treat these side effects.