Associations between early tumor shrinkage/depth of response and survivals from the ARCAD database.

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

Methods: We analyzed 3,219 treatment-naïve patients with RAS wild-type mCRC from eight randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Analysis and Research in Cancers of the Digestive System (ARCAD) database. ETS was defined as a ≥ 20% reduction in tumor size at 8 ± 2 weeks, whereas DpR was assessed by maximum tumor shrinkage at nadir. Cox regression models evaluated the associations of ETS and DpR with OS, PFS, and PPS, adjusting for confounders. A two-sided test was conducted with a significance level of 0.05.

Results: ETS and DpR significantly stratified OS, PFS, and PPS outcomes across all treatment groups. ETS positivity was associated with improved OS, PFS, and PPS in anti-EGFR and bevacizumab-based therapies, with a trend toward better outcomes in the anti-EGFR group. The DpR analysis revealed optimal cutoff values of 0.55 for anti-EGFR-based therapy and 0.47 for bevacizumab-based therapy to achieve a median OS of approximately 32 months.

Conclusions: ETS and DpR serve as valuable prognostic markers in RAS wild-type mCRC, particularly for patients treated with anti-EGFR antibodies. These findings highlight the potential role of ETS and DpR in guiding treatment strategies and improving patient outcomes.