4020 - Skeletal muscle loss as an adverse event during Cabozantinib treatment in patients with metastatic renal cell carcinoma

Background

Cabozantinib (CABO) is currently a standard of care as 2nd or 3rd line in metastatic renal cell carcinoma (mRCC). Previous studies showed that sarcopenia is generally linked with worse survival and/or higher toxicity in oncology. The aim is to evaluate its impact in mRCC patients (pt) treated with CABO.

Methods

Unicentric study of consecutive pt treated with CABO for mRCC from January 2014 to December 2018 and with available computed tomography images (CT). CT were centrally reviewed and axial L3 sections were used to measure the total muscle area and calculate skeletal muscle index (SMI, cm²/m²). Sarcopenia was defined as SMI lower than a sex-based threshold. Sarcopenic event-free survival was estimated from CABO start. Treatment-related toxicity (TRT), defined as dose reduction and/or treatment stop, was evaluated.

Results

Overall, 95 pts with median-follow-up of 15.4 months (mo) from CABO start were included. The median age was 61 (range 28-75) years, 71 (74.7%) pts had clear cell histology. IMDC group distribution: 11.7% good, 62.8% intermediate and 25.5% poor. CABO was administered in 1rd (3.2%), 2nd (30.5%), 3rd line (26.3%) and beyond (40.0%). At CABO start, median BMI was 24.7kg/m², median SMI was 46.6 with 61 (64.2%) sarcopenic pt. For non-sarcopenic pt at baseline (n = 34), 18 (52.9%) developed sarcopenia during treatment with a median sarcopenic event-free survival of 6.7 mo (95%CI 3.5-27.4). Overall, 79 (83.2%) pt experienced muscle mass loss during the treatment: the relative variation of muscle loss between baseline and worst value was ≤5% in 22.1%, ]5-10%] in 26.3%, ]10-20%] in 24.2% and >20% in 10.5%. The best response was CR (1.1%), PR (35.5%), SD (54.8%) and PD (8.6%). Median time-to-TRT was 2.5 mo (95%CI 2.1-3.3; 74.7% events) and median overall survival was 20.1 mo (95%CI 18.0-NE; 35.8% deaths). Both endpoints were not associated to sarcopenia at CABO start.

Conclusions

We reported the first cohort assessing sarcopenia in pt treated with CABO for mRCC. Baseline sarcopenia is underestimated in this setting. Furthermore, half of non-sarcopenic patients at baseline develop sarcopenia during treatment requiring physician awareness and interventional studies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Onco-urology department of Gustave Roussy.

Disclosure

E. Colomba: Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: PFIZER; Travel / Accommodation / Expenses: SANOFI. B. Escudier: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Oncorena. L. Albiges: Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Bristol‐Myers Squibb; Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Astellas Pharma. All other authors have declared no conflicts of interest.