OBJECTIVES: In the ongoing phase 3 CodeBreaK 300 trial, the efficacy and safety of sotorasib and panitumumab is compared with investigator’s choice (trifluridine/tipiracil, or regorafenib) in previously treated metastatic CRC (mCRC) patients with KRAS p.G12C mutation. Secondary and exploratory endpoints include the evaluation of health-related quality of life (HRQoL). To assess clinically important changes in HRQoL, reference values for minimally important differences (MID) are needed. This study reviewed the literature to identify MID thresholds established in CRC.

METHODS: A systematic literature review of observational and interventional studies was conducted (search performed on February 3, 2022) following the PRISMA 2020 guideline to identify MID thresholds in patient-reported outcome scores at the item, domain, or total score level in patients with CRC with specific focus on patients with mCRC and those with KRAS mutations.

RESULTS: Of the 8226 identified citations, 70 primary publications were included. MID thresholds were reported in 21 studies for mCRC patients and in 5 studies for mCRC patients with ≥2 prior lines of treatment. The EORTC QLQ-C30, EQ-5D, FACT-C, and FACT-G were the most often reported instruments in the identified literature. Most studies used MID thresholds that were already defined elsewhere. The most often reported MID threshold for EORTC instruments was 10 points for single items and subscales. The MID threshold for the EQ-5D instrument ranged from 5.48 to 12 points for the VAS, from 0.03 to 0.8 for the utility index, and from 0.2 to 0.5 for Cohen’s d effect size. The MID threshold ranged from 3 to 6 points for the FACT-G, and 5 to 8 points for the colorectal cancer-specific FACT-C questionnaire.

CONCLUSIONS: The most often reported MID threshold for the EORTC instruments was 10 points for all single items and subscales. No publications reported MID threshold for patients with KRAS mutations.