# Associations between early tumor shrinkage/depth of response and survival from the ARCAD database

## TL;DR

This study shows that early tumor shrinkage and depth of response are strong predictors of survival in patients with metastatic colorectal cancer treated with anti-EGFR or bevacizumab therapies.

## Contribution

The study identifies optimal cutoff values for depth of response in anti-EGFR and bevacizumab therapies to predict survival outcomes in RAS wild-type metastatic CRC.

## Key findings

- Early tumor shrinkage and depth of response significantly stratify survival outcomes across treatment groups.
- Anti-EGFR therapy showed a trend toward better outcomes compared to bevacizumab-based therapy.
- Optimal depth of response cutoffs of 0.55 and 0.47 predict a median overall survival of 32 months for anti-EGFR and bevacizumab therapies, respectively.

## Abstract

Early tumor shrinkage and depth of response have emerged as potential prognostic indicators in metastatic colorectal cancer (CRC). However, their associations with overall survival, progression-free survival (PFS), and postprogression survival in patients receiving anti–epidermal growth factor receptor (EGFR) antibodies or bevacizumab remain unclear.

We analyzed 3219 treatment-naive patients with RAS wild-type metastatic CRC from 8 randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Aid and Research in Digestive Cancerology database. Early tumor shrinkage was defined as a 20% or more reduction in tumor size at 8 ± 2 weeks, whereas depth of response was assessed by maximum tumor shrinkage at nadir. Cox regression models evaluated the associations of early tumor shrinkage and depth of response with overall survival, PFS, and postprogression survival, adjusting for confounders. A 2-sided test was conducted with a significance level of .05.

Early tumor shrinkage and depth of response substantially stratified overall survival, PFS, and postprogression survival outcomes across all treatment groups. Early tumor shrinkage positivity was associated with improved overall survival, PFS, and postprogression survival in anti-EGFR and bevacizumab-based therapies, with a trend toward better outcomes in the anti-EGFR group. The depth of response analysis revealed optimal cutoff values of 0.55 for anti-EGFR–based therapy and 0.47 for bevacizumab-based therapy to achieve a median overall survival of approximately 32 months.

Early tumor shrinkage and depth of response serve as valuable prognostic markers in RAS wild-type metastatic CRC, particularly for patients treated with anti-EGFR antibodies. These findings highlight the potential role of early tumor shrinkage and depth of response in guiding treatment strategies and improving outcomes for patients with CRC.