Regorafenib in patients with metastatic colorectal cancer in Spain: from clinical trials to real-world evidence.

Aim: To describe the evolution of regorafenib use, since its approval, in patients with previously treated metastatic colorectal cancer (mCRC) in routine clinical practice in Spain. Methods: We extracted patient characteristics, dosing, safety and efficacy data for the Spanish cohorts of the CORRECT and CONSIGN trials, and the real-world CORRELATE study. Results: The Spanish cohorts represented 10.7–13.8% of the global cohorts. Efficacy and safety in the Spanish cohorts reflected findings from the global cohorts, with evidence of a flexible dosing approach being adopted in routine clinical practice. Conclusion: Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients. Clinical trial registration: The CORRECT trial is registered at ClinicalTrials.gov, number NCT01103323; the CONSIGN trial is registered at ClinicalTrials.gov, number NCT01538680; the CORRELATE study is registered at ClinicalTrials.gov, number NCT02042144. Plain Language Summary Bowel cancer (also called colorectal cancer) affects the large bowel, including the colon and rectum. Approximately one in ten patients with advanced bowel cancer that has spread to other areas of the body (metastatic bowel cancer) survive 5 years after diagnosis or the start of treatment. Regorafenib is a treatment for patients with advanced bowel cancer that has continued to spread after receiving other treatments. It can slow down cancer growth, as shown in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, bowel cancer is the most common type of cancer and the cancer that causes the second most deaths. This study describes how the use of regorafenib in Spain has changed since it was approved in 2012, by looking at the patients from Spain who made up 11–14% of the participants in the three international studies. The CORRECT trial that compared regorafenib with a non-therapeutic placebo and the CONSIGN trial of regorafenib alone showed that treatment with regorafenib prolonged life and was well tolerated in patients with metastatic bowel cancer who had previously received or were not suitable to receive other treatments. The CORRELATE study showed that in the real world (i.e., outside of a controlled clinical trial), patients are sometimes prescribed regorafenib at lower starting doses than the recommended dose, without an apparent overall effect on how well regorafenib works or side effects. In the future, it will be important to continue researching how doctors prescribe regorafenib in daily clinical practice in Spain. Tweetable Abstract This article describes how #Stivarga use in Spain has evolved since its approval for metastatic #colorectalcancer, by analyzing data from Spanish patients enrolled in three international studies (CORRECT, CONSIGN and CORRELATE). In Spain, metastatic colorectal cancer (mCRC) is ranked first among cancers in terms of incidence and second in terms of mortality. An increasing number of patients with mCRC reaching third or further line therapy are able to receive additional treatment, including anti-tumor therapy. The oral multikinase inhibitor regorafenib was first approved in 2012, based on the results of the international, phase III randomized controlled trial CORRECT (NCT01103323). Safety was further evaluated in a larger population in the international, phase IIIb, single-arm trial CONSIGN (NCT01538680). Safety and efficacy were subsequently evaluated in an unselected, real-world population of patients in the international, prospective, observational CORRELATE study. This report presented data for the Spanish cohorts of these three prospective studies, representing 10.7–13.8% of the corresponding global cohorts. Overall, efficacy and safety in the Spanish cohorts reflect the findings from the corresponding global cohorts. Importantly, a proportion of the Spanish cohort of CORRELATE initiated treatment at a dose lower than the approved 160 mg/day, with 9.1% of patients starting at 120 mg/day and 7.7% starting at 80 mg/day. These three studies, separated by time, design and sample size, showed that a flexible dosing approach has been adopted in routine clinical practice since initial regorafenib approval. Regorafenib use in patients with mCRC has evolved in the real-world setting, emphasizing the need for further research evaluating dosing patterns that can optimize clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]