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. 2022 Oct;13(5):2405-2416.
doi: 10.1002/jcsm.13021. Epub 2022 Jul 28.

Weight and skeletal muscle loss with cabozantinib in metastatic renal cell carcinoma

Emeline Colomba  1 , Carolina Alves Costa Silva  1   2 , Gwénaël Le Teuff  3   4 , Jamie Elmawieh  5 , Daniel Afonso  6 , Axelle Benchimol-Zouari  6 , Annalisa Guida  7 , Lisa Derosa  1   2 , Ronan Flippot  1 , Bruno Raynard  8 , Bernard Escudier  1 , François Bidault  6 , Laurence Albiges  1
Affiliations

Weight and skeletal muscle loss with cabozantinib in metastatic renal cell carcinoma

Emeline Colomba et al. J Cachexia Sarcopenia Muscle. 2022 Oct.

Abstract

Background: Cabozantinib, a standard of care metastatic renal cell carcinoma (mRCC), may be associated with weight and muscle loss. These effects of new generation VEGFR tyrosine kinase inhibitor on muscle mass loss are poorly described.

Methods: All cabozantinib-treated mRCC patients from January 2014 to February 2019 in our institution were included. Clinical data including weight were collected during therapy. Computed tomography images were centrally reviewed for response assessment, and axial sections at the third lumbar vertebrae were used to measure the total muscle area. Toxicities and cabozantinib outcomes were evaluated. Co-primary endpoints included skeletal muscle loss and weight loss (WL), longitudinally evaluated during treatment. WL has been classified according to CTCAEv5.0: Grade 1 (loss of 5 to <10% of baseline body weight), Grade 2 (loss of 10% to <20% of baseline body weight), and Grades 3-4 (loss >20% of baseline body weight).

Results: Patients were mostly men (70.3%), median age was 59.2 (range: 22.0-78.0) years, and median baseline body mass index was 25.0 (range: 16.4-49.3) kg/cm2 . Prognosis according to International Metastatic RCC Database Consortium score was good, intermediate, and poor for 13 (13.0%), 63 (63.0%), and 24 (24.0%) patients, respectively. Out of a total of 120 patients, 101 patients with a median follow-up of 22.3 months (range: 4.5-62.2) were eligible for analysis; 85 experienced muscle loss and muscle loss >10% increased during cabozantinib exposition, especially after 6 months of treatment. At cabozantinib baseline, 71 patients (70.3%) had sarcopenia, and 16/30 (53.3%) non-sarcopenic patients developed sarcopenia during treatment. Baseline sarcopenia was associated with lower response rates (P = 0.031) and higher grades 3-4 toxicities (P = 0.001). Out of 92 patients included in the WL analysis, 44 (47.8%) and 12 (13.0%) experienced grades 2 and 3 WL, respectively.

Conclusions: We report a high incidence of grades 3-4 WL, fourth times higher than reported in prior pivotal trials, and half of the patients developed sarcopenia while on cabozantinib treatment. Weight and muscle mass loss with cabozantinib are underreported and may require further investigations and early management.

Keywords: Cabozantinib; Metastatic renal cell carcinoma; Muscle wasting; Sarcopenia; Weight loss.

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Conflict of interest statement

E.C. declared consulting or Advisory Role: Ipsen, Sanofi, GSK, Merck, BMS and Pfizer. R.F. declared consulting BMS, Ipsen. B.R. received honoraria as a lecturer from Baxter, Fresenius Kabi, Nestle Health Science, Nutricia, and Amgen. B.E. declared consulting or Advisory Role: Bristol‐Myers Squibb, Ipsen, Roche, Pfizer, Oncorena, Aveo. L.A. declared consulting or Advisory Role: Novartis, Amgen (Inst), Bristol‐Myers Squibb, Bristol‐Myers Squibb (Inst), Ipsen (Inst), Roche (Inst), Novartis (Inst), Pfizer (Inst), Astellas Pharma (Inst), Merck (Inst). A.B.Z., F.B., C.A.C.S., L.D., G.L.T., E.J., and D.A. declared no disclosures.

Figures

Figure 1
Figure 1
Patients flowchart.
Figure 2
Figure 2
Maximal relative change of weight loss (n = 92) (A) and skeletal muscle (n = 101) (B) from baseline during cabozantinib treatment.
Figure 3
Figure 3
Progression‐free survival (A), overall survival (B), dose‐modification‐free survival (C), and treatment‐failure‐free survival (D) according to sarcopenia at baseline.
Figure 4
Figure 4
Swimmer plot of non‐sarcopenic patients at cabozantinib initiation (n = 30). PD, progression disease; PR, partial response; SD, stable disease.
Figure 5
Figure 5
Scatter plot of the weight and skeletal muscle. Each dot with the same colour represents paired data (weight & muscle skeletal) for a patient with the corresponding line showing the repeated measure correlation fit for each patient.
See this image and copyright information in PMC

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