Late COVID-19 metastatic colorectal cancer therapy: to start or to delay?

Abstract

In the context of the COVID-19 pandemic, the multikinase inhibitor regorafenib is an important option for systemic treatment of metastatic colorectal cancer (mCRC) after oxaliplatin, irinotecan, and fluoropyrimidine ± biologics. Regorafenib inhibits various protein kinases implicated in oncogenesis, angiogenesis, and the tumour microenvironment. In two placebo-controlled, randomized, phase III trials treatment with regorafenib was associated with prolonged overall survival and progression-free survival in heavily pretreated patients and clinical benefit was consistent across various patient subgroups. The benefit provided by regorafenib was confirmed in observational studies designed to characterize safety and effectiveness in an unselected, real-world population of patients with mCRC. Both immunotherapy (atesolizumab) or combination of target plus immunotherapy (cobimetinib plus atezolizumab) did not prolong overall survival compared to regorafenib in phase III trial IMblaze, where regorafenib was used as the standart of care in the control arm because it is approved globally in the treatment setting tested in the study. New data show that regorafenib can positively interfere with the immunosuppressive state, increasing the immunosensitivity of the tumor or the tumor microenvironment. Regorafenib has increased activity in earlier lines of therapy vs later lines of therapy (when patients tend to benefit to a lesser degree) and clinical date provide evidence for the use of regorafenib before chemotherapy rechallenge or anti-EGFR monotherapy.