The Food and Drug Administration (FDA) has approved a highly effective immunotherapy drug combination for the treatment of clear cell metastatic kidney cancer. Results from Checkmate-214, an international phase three clinical trial with more than 1,000 participants, were published in the New England Journal of Medicine in April 2018.
This drug combination could potentially benefit over 50 percent of all metastatic kidney cancer patients. Patients in the trial had aggressive, quickly growing cancers – approximately 40 percent were considered intermediate-risk and 40 percent were considered poor-risk.
Data from Checkmate-214, which was co-led by Hans Hammers, M.D., Ph.D., revealed that the combination of immunotherapy drugs ipilimumab and nivolumab improved response rates from 27 percent with sunitinib, which is the current standard of care, to 42 percent. Additionally, 9 percent of the responses were complete, eliminating all traces of the cancer. Furthermore, the combination treatment improved patients’ quality of life.
Details about the new drug combination
Ipilimumab and nivolumab are given intravenously every three weeks for four cycles. Then patients switch to a single drug, nivolumab, which is given every two or four weeks for up to two years. The majority of patients in the study experienced an early, positive response, and these patients tend to do well with long-term treatment. In Checkmate-016, the precursor study to Checkmate-214 that was led by Dr. Hammers, a similar response rate was found, and 40 percent of the responses lasted two years.
It’s too early to consider the combined drug to be curative. However, we can say with confidence that it does have curative potential – patients can come off the therapy and do well for long periods of time. Based on initial data from the precursor study of nearly 100 patients with different doses of the drug combination, it seems that around 10 percent of patients or more may not progress for years.
Quality of life benefits balanced with risks
Patients who received the combination drug reported higher quality of life scores than patients who received sunitinib. Interestingly, quality of life actually improved during treatment and remained higher than at baseline after two years.
Every patient in Checkmate-214 received a survey regarding their quality of life concerning symptoms such as bone pain; diarrhea and nausea; fatigue; cough; decreased appetite and weight loss; fever; hand-foot syndrome; sleep loss; metallic taste; and weakness. Patients who were treated with the immunotherapy combination felt better.
That said, there are risks involved with the combination immunotherapy that require expertise from specialized doctors. The immune system may attack normal cells as well as cancer cells. Such reactions include:
● Colon inflammation
● Lung inflammation
● Liver inflammation
● Problems with hormone-producing organs (e.g., the thyroid or pituitary glands)
● Skin rash
Approximately 40 percent of patients require significant doses of immune suppressive steroids to control these symptoms. During Checkmate-214, 22 percent of patients had to stop taking the combined drug due to side effects. However, many of these patients still saw benefits insofar as their tumors were reduced in size even after treatment was ceased – often leading to prolonged periods which required no further treatments.
However, other rare and serious side effects may occur, including neuropathy leading to loss of nerve function, cardiomyopathy leading to heart failure, and even death. It is vital, especially early in treatment, for patients to be managed by immunotherapy experts. Side effects should be treated promptly when they arise. Additionally, patients who want to try immunotherapy must have a thorough understanding of the risks, as patients’ side effects could be quite serious or life-threatening, in more severe cases.
Without question, this new drug combination is a significant advancement in kidney cancer therapy.
Options for good-risk patients with kidney cancer
This drug combination gives hope for patients with aggressive metastatic kidney cancers. However, nearly 30 percent of patients overall are considered good-risk because their tumors grow slowly, and the combination drug is not FDA-approved in this patient population. In this group of patients, kidney cancers appear to be less inflamed and to benefit less from immunotherapy in comparison to sunitinib. Nonetheless, 10 percent of patients are seeing their cancers completely disappear even among those with good-risk disease. For this reason, the guidelines of the National Comprehensive Cancer Network (NCCN) list the combination drug as a treatment option for patients with good-risk disease as well.
The question then becomes whether the risk-benefit ratio is favorable enough to treat good-risk patients with ipilimumab and nivolumab. While there is a 10 percent chance that good-risk patients could have a complete response with the combined drug – and encouraging responses have been seen in good-risk patients who’ve elected to try it – we need more data to determine its true effectiveness in this group. In addition, overall response rates were significantly higher with sunitinib in this patient population – 52 percent compared to 29 percent with combination immunotherapy. Patients are encouraged to discuss these nuances in detail with their oncologists.
Patients with kidney cancer can access advanced care from internationally recognized experts at the UT Southwestern Kidney Cancer Program. Our doctors approach kidney cancer treatment as a team to ensure every patient receives personalized care with the most positive outcome possible. Meet our kidney cancer and immunotherapy experts.
Patients’ five-year survival rates are superior to national benchmarks, including more than double for patients with stage 4 cancer. This is likely the result of multiple factors, including expertise in the disease, a team approach, and access to the latest treatments in clinical trials.
The future of immunotherapy for kidney cancer treatment
Ongoing research studies will help us further refine and enhance kidney cancer immunotherapy. For example, Dr. Hammers is currently conducting a study that pairs ipilimumab and nivolumab with radiation (RADVAX trial), and initial data suggest that this approach might be even more effective than the combination drugs alone. The radiation inflames and destroys a chosen tumor, thus creating a vaccine inside the patient’s body.
In addition, building upon Nobel-prize winning discoveries by Bruce Beutler, M.D., at UT Southwestern, a trial has opened to evaluate a promising immunotherapy drug combination that may increase the number of tumors that can be controlled with immunotherapy. The trial, which is sponsored by Nektar Therapeutics and led by Dr. Brugarolas at UT Southwestern, evaluates a toll-like receptor (TLR) agonist in combination with a cytokine (IL-2) and nivolumab. The combination may turn ‘cold’ tumors into ‘hot’ inflamed tumors that can be detected and eliminated by the immune system.
Immunotherapy is becoming a household term, due in part to marketing efforts on television and online. Without question, this new drug combination is a significant advancement in kidney cancer therapy.