Sarah Elizabeth Yentz, MD, clinical assistant professor, University of Michigan Health, discusses treatment considerations in patients with favorable-risk renal cell carcinoma (RCC).

Patients classified as having favorable-risk RCC represent approximately 20% of RCC cases and have disease characteristics that are distinct from those of other RCC risk sugroups, Yentz says. Therefore, treatment options for patients with favorable-risk RCC often include approaches that may not be optimal in patients with poor-risk disease who are symptomatic and need immediate treatment, Yentz notes. The initial consideration for patients with favorable-risk RCC is whether treatment is necessary at all, as a subset of patients with very low-volume disease can be safely observed, Yentz explains. For instance, some data support active surveillance as an appropriate approach in patients with low-volume disease exhibiting slow tumor growth, according to Yentz.

Another disease management strategy for favorable-risk patients is oligometastatic treatment, Yentz elaborates. This historically involved surgical intervention, but advances in stereotactic body radiation therapy (SBRT) now enable precise, radiation-based treatment in small, localized metastatic lesions, Yentz says. For example, SBRT can target 1 or 2 lesions in specific sites, such as the lungs, Yentz notes.

Regarding systemic therapies, the National Comprehensive Cancer Network (NCCN) guidelines do not recommend using ipilimumab (Yervoy) plus nivolumab (Opdivo) in favorable-risk patients, as clinical trial data from the phase 3 CheckMate 214 trial (NCT02231749) demonstrated a more pronounced efficacy benefit with the combination vs sunitinib (Sutent) in intermediate- and poor-risk patient subgroups compared with the favorable-risk subgroup, Yentz explains.

Many patients with favorable-risk RCC have favorable disease outcomes regardless of the treatment they receive, Yentz says. Additionally, some patients’ disease biologies may be more driven by VEGF than others’, and are thus more responsive to TKIs, Yentz emphasizes. However, the body of evidence from other clinical trials indicates that some favorable-risk patients exhibit durable responses with ipilimumab plus nivolumab and maintain disease control after stopping treatment, Yentz says. Although the NCCN guidelines do not list this combination as a standard of care for favorable-risk patients because of the design of CheckMate 214, it remains a valuable option to consider for patients with favorable-risk RCC, Yentz concludes.

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Sarah Elizabeth Yentz, MD, discusses treatment considerations in patients with favorable-risk renal cell carcinoma. 

Dr Yentz on Treatment Decisions in Favorable-Risk RCC

Sarah Elizabeth Yentz, MD, clinical assistant professor, Medical Oncology, Internal Medicine, the University of Michigan Rogel Cancer Center, discusses how she decides between an immunotherapy agent plus a TKI combination vs 2-agent immunotherapy for patients with renal cell carcinoma (RCC).

A patient with kidney cancer who's symptomatic and needs a quick response may benefit from an immunotherapy agent plus a TKI because the chance of response is generally higher with this combination, Yentz begins. Therefore, if a patient has intense symptoms, they should receive the treatment regimen that has the highest chance of working, she notes. Fortunately, many patients without intense symptoms have more time to think about treatment options. In those patients, treating oncologists consider immunotherapy monotherapy, Yentz explains.

Patients who receive immunotherapy/TKI regimens, generally receive the TKI for the rest of their lives, and continue the immunotherapy for at least 2 years, Yentz expands. However, some patients who receive 2-agent immunotherapy regimens, such as nivolumab (Opdivo) plus ipilimumab (Yervoy), respond well and can end their therapy earlier, she emphasizes.

As most immunotherapy and immunotherapy/TKI regimens are associated with similar overall survival (OS) outcomes, Yentz tends not to use OS as a measurement when deciding between the 2 approaches. The chance of having an immune-related adverse effect (AE) is higher with immunotherapy [than with TKIs], and these AEs tend to occur earlier, within the first 3 months of immunotherapy treatment, Yentz continues. However, the TKI-associated AEs are often more chronic and never go away, she notes. These AEs include hypertension and diarrhea, as well as rashes on hands and feet, she emphasizes. Dose modifications can increase the tolerability of TKIs, and patients can also take breaks from these treatments.

Overall, the efficacy and safety profiles of immunotherapy/TKI combinations and immunotherapy doublets should be considered when deciding between these 2 regimens, Yentz concludes.

Sarah Elizabeth Yentz, MD, discusses how she decides between an immunotherapy agent plus a TKI combination vs 2-agent immunotherapy for patients with renal cell carcinoma.

Dr Yentz on Treatment Decisions for Patients With Kidney Cancer

Sarah Elizabeth Yentz, MD, clinical assistant professor, University of Michigan Health, medical oncologist, Brighton Center for Specialty Care, Rogel Cancer Center, Michigan Medicine, discusses translating data to real-world clinical practice in renal cell carcinoma (RCC).

Several novel options have been added to the treatment paradigm for patients with RCC, so treatment selection among the different TKI plus PD-L1 inhibitor combinations can be challenging, Yentz says. Although the combinations are more similar than they are different, the toxicities associated with the TKIs or the way in which adverse effects present differ, Yentz explains. As such, becoming familiar with all the TKIs and their different adverse effects can be difficult, so it is important to get comfortable with a specific TKI, Yentz adds.

Moreover, understanding these differences between TKIs is important for the patient to receive optimized treatment, Yentz continues. For example, cabozantinib (Cabometyx) has a long half-life, which can be difficult when a patient is not tolerating treatment because their symptoms may not improve for a prolonged period, Yentz says. In contrast, axitinib (Inlyta) has a shorter half-life. Overall, considerations such as these emerge during the real-world utilization of these regimens and change from what the data from clinical trials say, Yentz concludes.

Sarah Elizabeth Yentz, MD, discusses translating data to real-world clinical practice in renal cell carcinoma. 


Dr. Yentz on Translating Data to Real-World Clinical Practice in RCC 

Sarah Elizabeth Yentz, MD, clinical assistant professor, University of Michigan Health, medical oncologist, Brighton Center for Specialty Care, Rogel Cancer Center, Michigan Medicine, discusses unmet needs in metastatic renal cell carcinoma (mRCC).

Historically, patients with mRCC received a TKI followed by immunotherapy or immunotherapy followed by a TKI, Yentz explains. However, now that immunotherapy is being combined with TKIs, it is harder to select the optimal treatment approach for a patient who progresses beyond first-line therapy, Yentz says. Moreover, the second-line setting is an area with room to incorporate new therapies ​because patients continue to progress on regimens that are now utilized in the frontline setting, Yentz adds.

Ultimately, it is important to have a plan for a patient’s treatment course to guide what therapy is optimal upon progression, Yentz concludes.

Sarah Elizabeth Yentz, MD, discusses unmet needs in metastatic renal cell carcinoma. 


Dr. Yentz on Unmet Needs in Metastatic RCC 


Sarah Elizabeth Yentz, MD, clinical assistant professor, University of Michigan Health, medical oncologist, Brighton Center for Specialty Care, Rogel Cancer Center, Michigan Medicine, discusses navigating frontline treatment selection in renal cell carcinoma (RCC).

It can be difficult to select between available frontline regimens for patients with RCC. Moreover, patients are often eligible for several regimens, which further complicates treatment selection, Yentz explains. 

For young patients with a low volume of disease, ipilimumab (Yervoy) in combination with nivolumab (Opdivo) is preferred because it can elicit durable complete responses, Yentz says. The combination regimens of immunotherapy and TKIs are preferred for patients with symptomatic, rapidly progressing disease because the rate of primary progression is lower with these doublets vs with ipilimumab/nivolumab. 

Notably, many patients are candidates for ipilimumab/nivolumab and immunotherapy/TKI regimens, so treatment selection should be based on other factors, such as patient comorbidities and disease characteristics, in these situations, Yentz concludes.

Sarah Elizabeth Yentz, MD, discusses navigating frontline treatment selection in renal cell carcinoma.



Sarah Elizabeth Yentz, MD

Articles

Dr Yentz on Treatment Decisions in Favorable-Risk RCC

Dr Yentz on Treatment Decisions for Patients With Kidney Cancer

Dr. Yentz on Translating Data to Real-World Clinical Practice in RCC

Dr. Yentz on Unmet Needs in Metastatic RCC

Dr. Yentz on Navigating Frontline Treatment Selection in RCC