Background: Anti-epidermal growth factor receptor (EGFR) therapies including cetuximab are a key component of treatment for metastatic colorectal cancer (CRC) with Rat Sarcoma viral oncogene homolog (RAS) wild-type status. However, predictive biomarkers for anti-EGFR therapy beyond RAS status remain controversial. The Wnt signaling pathway, which is essential for embryonic development, becomes frequently dysregulated in the presence of APC mutations. Objectives: To evaluate the impact of APC mutation status on survival outcomes in patients with RAS wild-type CRC treated with cetuximab-containing chemotherapy Design: Single-center retrospective analysis Methods: We retrospectively analyzed patients with RAS wild-type metastatic CRC who received first-line cetuximab plus chemotherapy at Samsung Medical Center between February 2021 and June 2024. The status of the APC mutation was determined by next-generation sequencing (NGS). We evaluated the impact of APC mutation on the treatment of cetuximab-containing chemotherapy. Results: Among 104 RAS wild metastatic CRC patients with cetuximab-containing chemotherapy as first-line therapy, 75 (72%) had APC-mutant tumors and 29 (28%) had APC wild. The presence of liver metastases and primary tumor locations was significantly different between patients with APC mutation and wild type. No complete responses were observed, and partial response was achieved in 64 patients with APC-mutated tumors (85%) and 17 patients with APC wild type tumors (59%). There was a significant difference in the objective response rate (ORR) between patients with APC mutation and wild type ( p -value of 0.003). The disease control rate (DCR) was 89.7% for patients with APC wild type and 97.3% for the APC-mutant group. The median OS was not reached (95% CI, 31.5–NA) in patients with the APC mutation, whereas it was 37.3 months (95% CI, 23.4–NA) in those with APC-wild type tumors ( p = 0.024). Conclusion: This study showed that the status of APC mutation may be associated with clinical outcomes in patients receiving cetuximab-containing chemotherapy in RAS wild metastatic CRC. Further prospective studies are warranted to validate and incorporate APC mutation into clinical decision-making algorithms.
Kim et al. (Fri,) studied this question.