965PWeight loss is an underestimated adverse event with cabozantinib in patients with metastastic renal cell carcinoma (mRCC)

Abstract Background Cabozantinib (cabo) is a potent VEGFR-TKI currently approved in mRCC as a standard of care in second line or beyond. However, the incidence of grade 3-4 weight loss (WL) reported in pivotal trial seems underestimated. The aim was to evaluate the weight loss in real life under cabo. Methods All consecutive mRCC patients treated with cabo at a single institution from January 2014 to August 2018 were included. Patients with ascite/oedema were excluded. Weight was evaluated every month under cabo. Toxicities that may influence weight loss as diarrhea, nausea, anorexia, stomatite were collected. Individual profile, weigh change from baseline and time to first grade 2 WL(> 10%) and grade 3 WL(>20%) were described; disease control rate (CR+PR+SD) and objective response rate (CR+PR) according to RECIST 1.1. We analysed Grade 1, 2, 3 WL at 1, 3 and 6 months in patients without progression disease beyond 6 months of cabo. Results From 102 patients receiving cabo, 91 patients with a median follow-up of a 15.9 months [range: 1.2-58.7] were included: 69.2% male, median age: 62.0 [28.0-78.0] years and median baseline BMI: 24.8 [16.6-49.3] kg/m2. IMDC score was good, intermediate and poor in 12 (13.5%), 58 (65.2%) and 19 (21.4%), respectively. Median cabo treatment duration was 10.4 months [1-26.9]. At study cut off, n = 37 (40.7%) patients are still on treatment, 39 (42.9%) stopped cabo for disease progression and 15 (16.5%) for toxicity. Overall, 32 patients (35.1%) had more than 10% WL (grade 2) from baseline including 10 patients (11%) with more than 20% WL (grade ≥ 3). DCR was 96.4 [95%CI 89.8-99.3] and ORR was 34.9% [95%CI 24.8-46.2]. Median overall survival was 20.3 months. In responders to cabo more than 6 months (n = 59), cumulative incidence of grade 2 and grade 3 WL were respectively: 44.1% (n = 26) and 13.6% (n = 8). Median time to first grade 2 WL was 11.9 months. In this group, 11.3%, 42.9%, 47.6% of patients lost weigh more than 5% at 1, 3, 6 month compared to baseline under cabo. Conclusions Significant weight loss with cabozantinib is undereported in clinical trials compared to real world setting. It requires investigations and early management to anticipate sarcopenia in patients. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure E. Colomba: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (institution), Advisory / Consultancy: SANOFI. B. Raynard: Advisory / Consultancy, Research grant / Funding (self): Fresenius Kabi. B. Escudier: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: EXELIXIS; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: NOVARTIS; Honoraria (self), Advisory / Consultancy: Pfizer. L. Albiges: Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Pfizer. All other authors have declared no conflicts of interest.