Spanish Real-World Evidence Cabozantinib

Study Overview
=================
Brief Summary
-----------------
RCC (Renal Cell Carcinoma) is the most common form of kidney cancer, accounting for 2-3% of all adult malignancies and for 90% of all kidney cancers. The incidence of RCC has steadily increased over the past two decades, showing a plateau in recent years. Many patients with RCC remain asymptomatic until late disease stages and other patients have disease at diagnosis (metastatic RCC or mRCC). Recently, the tyrosine kinase inhibitor (TKI) cabozantinib was approved as a first-line therapy for patients with advanced clear-cell RCC (ccRCC). Cabozantinib was initially approved for patients previously treated with antiangiogenic therapy based on the phase 3 METEOR study, which demonstrated a clinical benefit compared with everolimus. Immunotherapy has been also developed in ccRCC. The frontline treatment paradigm for ccRCC has evolved, particularly for intermediate-/poor-risk patients, with the recent addition of cabozantinib and nivolumab/ipilimumab (immunotherapy), but overall survival data are needed to understand their benefit-to-risk profiles compared with established therapies. In October 2016, the Spanish Agency of medicines (AEMPS) granted the temporary Authorization for special use to Cabometyx® 20/40/60 mg within a Managed Access Program (MAP) for the treatment of advanced RCC in adults following prior VEGF-targeted therapy (Vascular Endothelial Growth Factor targeted therapy). The MAP allows the possibility of using a medicinal product which is not yet commercially available or approved. By the end of the MAP period, on July 2017, 136 patients had been included by 61 centers who received at least one dose of Cabometyx® for the treatment of advanced RCC. Since then, Cabometyx® 20/40/60 mg was made commercially available for the treatment of advanced RCC in adults following prior VEGF-targeted therapy. After the commercialization of Cabometyx® in July 2017 in Spain, the inclusion of new patients in the MAP was closed but those patients that were already included continued receiving Cabometyx® free of charge until clinical decision. In July 2018, the European Commission approved a new indication for adult patients previously untreated with intermediate or poor risk. Based on this rationale, the aim of this study is to obtain safety and effectiveness information regarding the use of cabozantinib in a non-selected RCC population, both in patients that received this agent under the MAP or under routine clinical prescription (real-world [RW]).

Official Title
-----------------
Study of the Effectiveness and Safety of Cabozantinib Treatment in Patients With Advanced Renal Cell Carcinoma (RCC) Under a Spanish Managed Access Program and Real-world Practice

Conditions
-----------------
Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Cabozantinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or females, aged 18 years or older. Diagnosis of advanced Renal Cell Carcinoma (RCC) Alive or dead patients at study initiation who received at least one dose of cabozantinib for the treatment of RCC between October 2016 and 1 st June 2019. Alive patients who agree to participate and signed the Informed Consent Form (ICF). Exclusion Criteria: Patients who decline consent. Patients whose hospital medical records are unavailable for review.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Managed Access Program (MAP) patients<br>Patients with RCC treated with cabozantinib under a Managed Access Program (MAP) prior to Cabometyx® marketing authorization | Drug: Cabozantinib<br>* Observation of treatment with Cabozantinib<br>|
| Real World (RW) patients<br>Patients with RCC treated with cabozantinib as routine clinical prescription (Real World), with treatment started after Cabometyx® marketing authorization | Drug: Cabozantinib<br>* Observation of treatment with Cabozantinib<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness: Progression-Free Survival | Evaluation of the effectiveness of cabozantinib in terms of investigator-assessed PFS (Progression-Free Survival) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Through study completion, an average of 2 years | 
| Incidence of Adverse Reactions | Evaluation of the safety of cabozantinib by recording the incidence of adverse reactions in both MAP and RW cohorts. | Through study completion, an average of 2 years | 
| Incidence of dose reductions | Evaluation of the safety of cabozantinib by recording the incidence of dose reductions in both MAP and RW cohorts. | Through study completion, an average of 2 years | 
| Incidence of temporary interruptions or discontinuations | Evaluation of the safety of cabozantinib by recording the Incidence of temporary interruptions or discontinuations in both MAP and RW cohorts. | Through study completion, an average of 2 years | 
| Incidence of use of medications to manage adverse reactions | Evaluation of the safety of cabozantinib by recording the incidence of use of medications to manage adverse reactions in both MAP and RW cohorts. | Through study completion, an average of 2 years |