Weighing the Catabolic Effects of Lenvatinib/Everolimus vs SOC in ccRCC

While combination therapy with lenvatinib (Lenvima) plus everolimus (Afinitor) offers superior progression-free survival (PFS) outcomes in metastatic clear cell renal cell carcinoma (ccRCC), newly presented data from the phase 2 LenCabo trial (NCT05012371) highlight a critical clinical trade-off. Findings revealed a pronounced catabolic effect associated with the regimen, including significantly greater reductions in body mass index (BMI), skeletal muscle mass index, and subcutaneous adiposity at 4 months compared with cabozantinib (Cabometyx).

In an interview with CancerNetwork®, María Teresa Bourlon, MD, MSc, FASCO, emphasized that these findings carry major implications for regimen selection, particularly among older or vulnerable patient populations. She noted that treatment-induced muscle and weight loss can exacerbate frailty, reduce physical strength, and impair quality of life, potentially leading to dose adjustments. Ultimately, Bourlon underscored the need for clinicians to carefully evaluate baseline patient fitness and body composition when weighing therapeutic options in this setting.

Bourlon is head of the Urologic Oncology Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico.

Transcript:

CancerNetwork: The LenCabo findings showed that although lenvatinib plus everolimus previously exhibited superior PFS over cabozantinib, it was also associated with significantly greater reductions in BMI, skeletal muscle mass index, and subcutaneous adiposity at 4 months. How should that catabolic signal factor into regimen selection, particularly for patients who are older or frailer?

Bourlon: These are important data. Whenever we’re prescribing a tyrosine kinase inhibitor [TKI] in any line of treatment for RCC, we’re concerned about its catabolic effect, especially reducing muscle mass and the [strength] of the patient. These [LenCabo] data, a combination therapy of lenvatinib plus everolimus vs cabozantinib, speak about what to expect for the patient—these results tell us that we could expect patients to become more frail and to lose their muscle mass and strength.

This is a real concern when we have in front of us an older patient from a geriatric population, a [patient who is] frail, or a patient who has lost a lot of weight. This is a significant toxicity that may impact outcomes, may preclude patients from receiving a full dose, and may even impact their quality of life because they’re not going to be able to do their daily activities. We’re lacking better measurements in the clinic to really see the impact of these medications on musculoskeletal toxicity, but this abstract is really informative to help us rethink whether we need to give this combination to patients who are frail, older, or who have lost a lot of muscle mass.

Reference

Moura J, Chahoud J, Skelton WP IV, et al. Body composition and quality of life (QOL) with lenvatinib + everolimus (len + eve) vs cabozantinib (cabo) in metastatic clear cell renal cell carcinoma (ccRCC) after PD-1 inhibitor progression: results from the randomized phase II LenCabo trial. J Clin Oncol. 2026;44(suppl 16):4538. doi:10.1200/JCO.2026.44.16_suppl.4538