Relationships Between Köhne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer

Abstract Background In metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics. Methods Data from patients with RAS wild-type mCRC who had participated in the PRIME (NCT00364013) and PEAK (NCT00819780) studies were analyzed retrospectively. ETS and DpR were assessed by baseline Kohne category/BRAF status (PRIME) and baseline tumor load (pooled PRIME and PEAK). Results Analysis populations included 436 to 665 patients. Patients’ chances of achieving ETS ≥30% were 63.8%, 50.4%, and 41.9% in the low-, medium-, and high-risk Kohne categories, and 21.7% in those with BRAF mutations. Corresponding percentages for the highest DpR classification (71%–100%) were 47.7% (low risk), 23.6% (medium risk), 10.0% (high risk), and 4.2% (BRAF mutant). No clear relationship was observed between baseline tumor load and ETS or DpR. ETS ≥30% and higher DpR values were associated with statistically significant prolongation of median progression-free survival (PFS) and overall survival (OS). Conclusion Patients with mCRC categorized at baseline by the Kohne criteria as high risk or with BRAF mutations have lower chances of achieving ETS ≥30% or a high DpR. Conversely, baseline tumor load was not predictive of ETS or DpR. Favorable ETS or DpR is associated with improved PFS and OS. Microabstract: In metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics. We assessed ETS and DpR by baseline Kohne category and tumor load (n=648). Patients categorized as high risk or with BRAF mutations have lower chances of achieving ETS ≥30% or a high DpR. ETS ≥30% and high DpR were associated with prolonged survival. Baseline tumor load was not linked with achieving ETS ≥30% or high DpR.