About the safety of lenvatinib (Lenvima)/everolimus and cabozantinib

The safety issues of lenvatinib/lenvatinib/everolimus and cabozantinib have gradually become an important focus of discussion in the treatment of metastatic clear cell renal cell carcinoma (ccRCC) in recent years. At the 2025 Medical Oncology Congress, the research results of the LenCabo trial (NCT05012371) were officially announced, providing a more systematic and prospective evidence-based basis for this issue. This study further improves the evidence system for the treatment of advanced ccRCC by directly comparing the efficacy and safety of Lenvima combined with everolimus (Afinitor) and cabozantinib (Cabometyx) monotherapy.

From an efficacy perspective,The LenCabo trial showed that lenvatinib combined with everolimus can significantly extend the progression-free survival of patients compared with cabozantinib. This result once again confirms the potential advantages of targeted combination therapy in renal cell carcinoma. However, in clinical practice, the selection of treatment options not only relies on efficacy benefits, but also pays close attention to patient tolerance and overall safety performance. Therefore, this study has important practical significance for the systematic evaluation of adverse events.

A total of 86 patients with metastatic clear cell renal cell carcinoma were included in the LenCabo trial, of whom 40 received lenvatinib in combination with everolimus and 46 received cabozantinib. The results showed that 67.5% of patients in the combination treatment group experienced grade 3 or 4 adverse events, compared with 50% of patients in the cabozantinib group. Although the incidence of adverse events was numerically higher in the combination regimen, statistical analysis showed that the difference between the two groups did not reach significance (OR 2.08; 95% CI, 0.86–5.02). This result suggests that while the combination regimen increases a certain toxicity burden, its overall safety is still within a controllable range.

No statistically significant differences were also observed between the lenvatinib/everolimus and cabozantinib groups in terms of more serious safety outcomes, such as adverse reactions leading to treatment discontinuation or significant impact on the patient's overall status. Study data showed that approximately 20% of patients in the combination treatment group experienced serious adverse events, compared with 11% in the cabozantinib group (OR 2.05; 95% CI, 0.61–6.91). Although the combined regimen still shows a numerically higher trend, the confidence interval is wider, indicating that the sample size is limited and is not enough to draw a clear conclusion of increased risk.

Taken together,the safety results of the LenCabo trial show thatlenvatinibWhile the combination of everolimus improved progression-free survival, it was indeed accompanied by an increasing trend in the incidence of adverse events, but the overall toxicity level was not significantly higher than that of cabozantinib monotherapy, and no new and unpredictable safety signals emerged. This finding has important reference value for clinicians when weighing efficacy and tolerability and formulating individualized treatment strategies for ccRCC patients with different risk characteristics. With the release of subsequent real-world data and larger sample studies, the safety differences between lenvatinib/everolimus and cabozantinib are expected to be further clarified, providing a more solid basis for precision treatment of metastatic renal cell carcinoma.

References: UpdatedNovember 14, 2025, https://www.urologytimes.com/view/andrew-hahn-md-on-the-safety-profile-for-lenvatinib-everolimus-vs-cabozantinib