Background: Cabozantinib is a tyrosine kinase inhibitor (TKI) directed against VEGFR, MET and AXL. In the pivotal phase III METEOR study, cabozantinib demonstrated significantly improved progression-free survival (PFS), overall response rate (ORR) and overall survival (OS) versus everolimus in patients with previously treated aRCC with clear-cell component. Thus, cabozantinib received marketing authorization from the European Medicine Agency in September 2016 for the treatment of aRCC in patients previously treated with a VEGF-targeted therapy. Cabozantinib effectiveness and safety have been investigated in several real-world evidence studies such as CABOREAL or CASSIOPE. However, many questions arising during the routine care of patients with aRCC treated by cabozantinib remain unanswered by the current literature. Therefore, the aims of OCTOPUS study are to describe the effectiveness and safety of 2^nd line cabozantinib in a real-life setting in France and to address these unanswered questions in certain patients subgroups. Methods: Octopus is a multicenter (25 centers), retrospective, non-comparative, non-interventional study in patients with aRCC initiating cabozantinib in 2^nd linein France. The primary endpoint is the duration of treatment (DOT) with cabozantinib: median DOT will be estimated using Kaplan Meier method. Key secondary endpoints to be assessed are: best overall response (BOR), PFS, adverse events (AEs) and subsequent treatment. DOT, BOR, PFS, safety and all baseline characteristics for each of the following subgroups will be described as exploratory endpoints: sequencing post-cabozantinib, long-responders, non-responders, cabozantinib & rechallenge, cabozantinib & therapeutic schedules, cabozantinib & local treatment, cabozantinib & elderly patients. Data will be analyzed descriptively. Due to the observational nature of this study, no formal calculation of sample size and statistical power were performed. With a sample size of 300 participants who started cabozantinib in 2^nd linebetween 1^st March 2018 and 1^st March 2021 and a median DOT of 7.6 months, the two-sided confidence interval of the median will be estimated with a width equal to 1.7 months (95% Confidence Interval [CI] [6.8; 8.6]) and a censoring probability near 0. All collected data will be in accordance with the daily practice of medical doctors, with a maximum follow-up of 12-months. Data collection started in Q3 2022 and the first patient was included on September 16^th 2022. No interim analysis is planned. This study is funded by Ipsen Pharma. Clinical trial information: NCT05444933.