Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

Abstract

Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.

Single Center Real Life Experience with Regorafenib in Patients with Metastatic Colorectal Cancer

“…Because of our small sample, further studies involving more patients are needed to confirm this information. life data, regorafenib was associated with a survival similar to that reported in the randomized controlled trials (7)(8)(9)(10)(11).…”

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

“…These drugs have been extensively used in patients with colon cancer, particularly when patients receive anti-VEGF-based chemotherapy combinations that might lead to increased blood pressure. Development of high blood pressure in metastatic Colorectal Cancer (mCRC) patients treated with anti-VEGF drugs has been described as a surrogate of better outcome for treated patients [ 7 , 8 ], thus leading to difficult treatment choices when deciding to lower blood pressure.…”

A Systematic Review and Meta-analysis of Retrospective Series of Regorafenib for Treatment of Metastatic Colorectal Cancer

“…Thirty-two retrieved articles were clinical trials or series. After exclusion of 12 reports describing phase I, II and III trials and eight case reports or series with few patients, 12 retrospective series remained to be included in the current analysis (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). These reports were published between 2015 and 2017 and described a total of 702 patients (Table I).…”

“…The preponderance of reports came from Asian populations, thus making the relevance of results for other populations debatable. Nevertheless, two out of the three most extensive series (22,25) accounting for more than half of the total patients analyzed were from Europe.…”