Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses the role of TKI monotherapy in the first-line treatment of patients with metastatic renal cell carcinoma (mRCC).

The phase II CABOSUN trial demonstrated an improvement in progression-free survival (PFS) and overall survival with cabozantinib (Cabometyx) versus sunitinib in patients with poor- or intermediate-risk disease. In the phase III CheckMate-214, KEYNOTE-426, and JAVELIN Renal 101 trials, investigators reported at least a PFS benefit compared with sunitinib with the combinations of ipilimumab (Yervoy)/nivolumab (Opdivo), pembrolizumab (Keytruda)/axitinib (Inlyta), and axitinib/avelumab (Bavencio), respectively, in patients with advanced RCC. 

As such, sunitinib should not be considered for first-line treatment of mRCC, says Ho. Though, the CABOSUN data suggest that cabozantinib could be an option for patients who are intolerant of or ineligible for immunotherapy, concludes Ho.

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Thai H. Ho, MD, PhD, discusses the role of TKI monotherapy in the first-line treatment of patients with metastatic renal cell carcinoma. 

Dr. Ho on First-Line TKI Monotherapy in mRCC

Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses frontline treatment regimens in metastatic renal cell carcinoma (mRCC).

There are two schools of thought when it comes to frontline treatment in mRCC, says Ho. The first is that patients should be stratified according to their risk and treated accordingly. In order to achieve a higher likelihood of complete response, the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) may be preferable to an alternative regimen for patients with intermediate- and poor-risk disease, adds Ho.

Another school of thought is to give the combination of axitinib (Inlyta) and pembrolizumab (Keytruda) to all comers, regardless of a patient’s International Metastatic RCC Database Consortium risk score. Notably, this combination has a higher objective response rate and a lower incidence of grade 3/4 adverse events than some of the other treatment regimens in the frontline setting. Dosing schedules may also factor into the decision, concludes Ho.

Thai H. Ho, MD, PhD, discusses frontline treatment regimens in metastatic renal cell carcinoma.

Dr. Ho on Frontline Treatment Regimens in mRCC

Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses the management of immune-related adverse events (AEs) in the treatment of patients with kidney cancer.

One of the things for genitourinary oncologists to keep in mind is that checkpoint inhibitors have a distinct toxicity profile. When AEs like pneumonitis or autoimmune colitis are detected, Ho says it would be beneficial to start steroid treatment earlier rather than later. These AEs can progress if they aren’t treated in their early stages. There are some emerging data from French groups as well as Dana-Farber Cancer Institute suggesting that even if steroid treatment is used, the durable responses associated with immunotherapy can be maintained.

With tyrosine kinase inhibitors (TKIs), Ho says it’s important to remember that dose adjustment is a viable option when unmanageable AEs present themselves. The scheduling regimen of tyrosine kinase inhibitors can also be adjusted.

Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses the management of immune-related adverse events in the treatment of kidney cancer.

Dr. Ho on Managing Immune-Related AEs in Kidney Cancer

Thai H. Ho, MD, PhD, assistant professor of medicine, Mayo Clinic, discusses common molecular subtype and phenotype alterations in the epigenetic pathway that are used to predict response to treatment.

Molecular subtypes from the thermogravimetric analysis show that there are certain mutations that are recurrent in renal cell carcinoma; these include 

 which is the most common mutation, followed by 

. Certain types of epigenetic mutations are associated with a favorable response to immune therapy and are currently being studied.

There are also molecular phenotypes that are defined by poor and intermediate risk. These are phenotypes that can be defined based on routine lab work. The patients who were defined as poor and intermediate risk were the patients who were enriched in the CABOSUN study, which led to the approval of cabozantinib. Similarly, these patients were studied in the CheckMate-214 trial, and showed an improved response in combination with nivolumab (Opdivo) and ipilimumab (Yervoy).

Thai H. Ho, MD, PhD

Articles

Dr. Ho on First-Line TKI Monotherapy in mRCC

Dr. Ho on Frontline Treatment Regimens in mRCC

Dr. Ho on Managing Immune-Related AEs in Kidney Cancer

Dr. Ho on How Molecular Subtypes Affect Sequencing