Investigators have characterized the adverse reactions (ARs) resulting from the use of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma (aRCC) as well as how these ARs were managed.

“Clinicians play a critical role in the prompt identification and management of ARs in patients with aRCC treated with lenvatinib + pembrolizumab,” a team led by Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, concluded in a poster presented at IKCS Europe 2022. “Prompt management of ARs may potentially reduce treatment interruption(s) and/or lenvatinib dose reduction and allow patients to continue receiving therapy.”

Dr Motzer and colleagues analyzed data from the CLEAR trial, which demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy outcomes compared with sunitinib as first-line treatment for advanced RCC. In the trial, investigators randomly assigned patients to receive lenvatinib 20 mg once daily orally plus pembrolizumab 200 mg intravenously once every 3 weeks; lenvatinib 18 mg once daily orally plus everolimus 5 mg once daily orally; or sunitinib 50 mg once daily orally (4 weeks on/2 weeks off).

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The most common ARs (of any grade occurring in 30% or more of patients) were fatigue (63.1%), diarrhea (61.9%), musculoskeletal pain (58.0%), hypothyroidism (56.8%), hypertension (56.3%), stomatitis (43.2%), and decreased appetite (40.6%), the investigators reported. Hypertension was the most common grade 3 or higher AR (28.7%), followed by diarrhea (9.9%), and fatigue (9.4%).

As a result of ARs, interruptions of lenvatinib, pembrolizumab, or both occurred in 78% of patients receiving the combination treatment (lenvatinib, 73%; both drugs, 39%), Dr Motzer reported in a poster presentation. Clinicians reduced the lenvatinib dose in 69% of patients. Permanent discontinuation of lenvatinib, pembrolizumab, or both due to an AR occurred in 37% of patients (lenvatinib, 26%; pembolizumab, 29%; both, 13%).

The median time to the first dose interruption of lenvatinib was 4.14 months; the median time to dose reduction of lenvatinib was 1.87 months.

Dr Motzer and his colleagues noted that certain ARs, such as diarrhea, may be attributable to either lenvatinib or pembrolizumab at first onset. Therefore, to manage the AR appropriately, it is important to try to determine the causative agent. “The timing of first onset of such ARs may be critical in making this determination.”

They also advised, “Since lenvatinib is given daily and has a shorter half-life, dose interruption of the drug may be considered as a first-line approach to determine whether clinical resolution can be obtained. If there is no clinical improvement, an immune-mediated AR may be considered.”

“A proactive approach in addressing treatment-emergent ARs is critical when treating patients with lenvatinib + pembrolizumab,” the investigators concluded.


Motzer R, George S, Merchan JR, et al. Characterization and management of adverse reactions in patients with advanced renal cell carcinoma receiving lenvatinib + pembrolizumab (CLEAR Study). Presented at: IKCS Europe 2022, April 22-24, 2022, Antwerp, Belgium. Poster 22.

This article originally appeared on Renal and Urology News