Regorafenib monotherapy as second-line treatment of patients with RAS-mutant advanced colorectal cancer (STREAM): an academic, multicenter, single-arm, two-stage, phase II study

•Early-lines treatment of patients with RAS-mutant mCRC consists of chemotherapy and antiangiogenic agents.•STREAM evaluated regorafenib as second line for RAS-mutant mCRC, in terms of rate of patients progression-free at 6 months.•The primary endpoint of STREAM was not met. Regorafenib had no unexpected toxicity and did not preclude subsequent therapies.•A chemotherapy-free interval with regorafenib was beneficial in patients with good prognostic features.•Baseline [18F]-FDG PET/CT might be useful to select patients with favorable outcomes.