Long-term response of more than 9 years to regorafenib in a heavily pretreated patient with metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, with approximately 1.9 million new diagnoses and 935 000 deaths annually. Overall, there is accumulating evidence that receiving all available treatments leads to a survival advantage and, although tailored treatments might be appropriate for selected patients, the one-size-fits-all approach is still widely used in chemo-refractory patients. Currently, different antiangiogenics and multitarget agents are indicated in treatment of metastatic CRC (mCRC) whereas the identification of useful predictive factors for the treatment response is lacking. Analysis of potential predictive biomarkers of efficacy of regorafenib is still ongoing but may prove to be difficult because of its nonspecific activity across a wide range of angiogenic, oncogenic, stromal, and intracellular signaling kinases. We present a case of a 57-year-old Caucasian woman diagnosed with recurrence after curative surgery for rectal adenocarcinoma stage III (ypT3N2). Despite undergoing multiple lines of standard chemotherapy, disease control could not be maintained. Consequently, regorafenib, a multikinase inhibitor with antiangiogenic proprieties, was started as a late-line treatment and a dose reduction strategy allowed a long-term response of more than 9 years with good tolerability.

Evaluation of Fruquintinib in the Continuum of Care of Patients with Colorectal Cancer

“…Every effort should be made to identify clinical and molecular biomarkers predictive of response. Potential factors associated with treatment response to antiangiogenics and multitarget agents included LDH, hERG1/aHIF-2α expression, the circulating angiopoietin-2 level, but results should be confirmed in prospective studies [ 27 , 48 , 49 , 50 , 51 ]. An exploratory analysis from the CORRECT trial showed an association between HFS reaction and survival benefit from regorafenib, and a similar differential benefit was observed for fruquintinib in a post-hoc analysis of the FRESCO trial [ 52 , 53 ].…”

“…Its efficacy in heavily pretreated patients may be due to the broad spectrum of anti-kinase activity, which conversely, may imply a higher incidence of adverse events (AE). However, a narrower range of targets might minimize off-target toxicities and improve the clinical outcome due to a higher drug exposure at the maximum tolerated dose (MTD) [ 26 , 27 , 28 , 29 , 30 , 31 ].…”