OBJECTIVES: To characterize grade 3/4 adverse event (AE) rates associated with fruquintinib, regorafenib, trifluridine/tipiracil (T/T), and trifluridine/tipiracil+bevacizumab (T/T+bev) for previously treated – with at least two prior lines – metastatic colorectal cancer (mCRC) using drug exposure-adjusted event rates (EAERs) to inform payer formulary and pathway decisions.

METHODS: Grade 3/4 AEs occurring in at least 5% of patients for any treatment in an individual trial were identified from Phase III randomized clinical trial publications FRESCO and FRESCO-2 for fruquintinib (N=734), RECOURSE and SUNLIGHT for T/T (N=779), CORRECT for regorafenib (N=500), and SUNLIGHT for T/T+bev (N=246). Treatment durations reported in the same clinical trials were converted to total treatment days (1 month = 30.325 days). AE incidence rates were then calculated to reflect an occurrence per 100 and per 1,000 treatment-days for each treatment.

RESULTS: Grade 3/4 AE occurring in at least 5% of patients for any treatment included: anemia, asthenia, diarrhea, fatigue, hand foot syndrome, hypertension, leukopenia, neutropenia, rash, thrombocytopenia, and laboratory abnormalities (increased alanine aminotransferase, alkaline phosphatase level, aspartate aminotransferase, and total bilirubin). EAERs per 1,000 patient-days of treatment exposure were estimated to be 3.87 for fruquintinib, 17.33 for T/T, 16.70 for regorafenib and 4.19 for T/T+bev treatment arms. EAERs per 100 patient-days treatment exposure were estimated to be 0.387 for fruquintinib, 1.733 for T/T, 1.670 for regorafenib and 0.419 for T/T+bev treatment arms.

CONCLUSIONS: Patients with mCRC previously treated with at least two prior lines of therapy experienced lower treatment EAERs associated with grade 3/4 AEs when treated with fruquintinib vs. other treatment options. Population health and healthcare plans decision makers may consider the use of EAERS of as an additional quantification measure when reviewing formulary and pathway choices of emerging and existing systemic therapies for patients with mCRC.