The CLEAR Trial: Lenvatinib Plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma - Episode 4

Implications of the CLEAR Study in mRCC to Clinical Practice

Implications for treating patients with metastatic renal cell carcinoma with frontline lenvatinib plus pembrolizumab, based on the regimen’s performance in the CLEAR study compared with other options.

Chung-Han Lee, MD, PhD: The CLEAR study is a positive phase 3 clinical trial for patients with treatment-naïve metastatic kidney cancer. Based on the results of the CLEAR study, the combination of lenvatinib plus pembrolizumab received regulatory approval for this treatment population. When we think about postregulatory approval, then there are guideline recommendations. Lenvatinib plus pembrolizumab is a category 1 preferred agent for patients with either favorable intermediate or poor risk, so essentially all the risk categories for RCC [renal cell carcinoma]. Putting that in the broader context of the NCCN [National Comprehensive Cancer Network] Guidelines, for patients with favorable-risk disease, most of the regimens that have a category 1 designations and for favorable risk in the preferred category are TKI [tyrosine kinase inhibitor]–I/O [immuno-oncology] combinations, including lenvatinib plus pembrolizumab, axitinib plus pembrolizumab, and cabozantinib plus nivolumab. For intermediate and poor-risk patients, regimens that have category 1 preferred designations include the TKI–I/O combinations, including lenvatinib plus pembrolizumab, axitinib plus pembrolizumab, cabozantinib plus nivolumab, but also anti CTLA4plus PD-1 with the combination of ipilimumab plus nivolumab. This forms strong evidence for each approach.

Thinking about how we stratify patients to these approaches, we really have to do some degree of clinical stratification and try to tailor the efficacy we see for each regimen to the patients’ own goals. The data are never as complete as we would want because the trials were designed and the results are what they are. As we get further, we’ll get more information about some of the long-term effects. However, based on the need to treat patients now as opposed to waiting for long term data to be available, the way we often make a treatment decision is going to be based on the available data and prioritizing things like response rates vs known vs unknown durability of response.

Kiran Kehoe, RN, BSN, CCRN: In terms of determining specific adverse effects with the TKI–I/O combinations of lenvatinib-pembrolizumab, axitinib-pembrolizumab, and cabozantinib-nivolumab, it can be difficult because the adverse events are nonspecific to each regimen. In general, we expect to see some adverse events with the TKI medications—axitinib, lenvatinib and cabozantinib—and also adverse events related to immunotherapy with pembrolizumab and nivolumab. There really is no comparison to say that certain adverse events will occur with this regimen; the adverse events are quite broad. What I have seen most commonly in our clinical practice is that there are some adverse events that are across the board with these regimens. That includes diarrhea, high blood pressure, fatigue, mouth sores or mucositis, and decreased appetite. To provide a comparison is really hard. These regimens are related to the adverse events of TKIs or the adverse events of immunotherapies, but not specific to 1 regimen.

Transcript edited for clarity.