1. Cancer Center, Aichi Medical University, Nagakute, Japan
2. Cancer Treatment Center, Kochi Medical School Hospital, Kochi University, Nankoku, Japan
3. Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
4. Department of Translational Research and Developmental Therapeutics against Cancer, Yamaguchi University School of Medicine, Ube, Japan.
5. Department of Biostatistics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
6. Division of Laboratory, Yamaguchi University Hospital, Ube, Japan
7. Department of Oncology and Laboratory Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan
8. Tokai Central Hospital, Kakamigahara, Japan.
9. Kitakyushu General Hospital, Kitakyushu, Japan.
Background: Oxaliplatin and capecitabine (CapeOX) combined with cetuximab is rarely used to treat advanced and metastatic colorectal cancer (mCRC). The present study aimed to clarify the clinical benefits of this treatment regimen when used as a first-line therapy in patients with expanded RAS/BRAF/PIK3CA wild-type mCRC, using the data and tumor specimens from two previously published Phase II clinical trials.
Methods: The gene mutation status and clinical data of 102 patients with KRAS wild-type mCRC, who received either of CapeOX + cetuximab or FOLFOX + cetuximab, were analyzed. The primary endpoint was response rate (RR) of CapeOX + cetuximab treatment in patients with extended RAS/BRAF/PIK3CA wild-type mCRC. RR comparisons and maximum tumor size changes between different treatment regimens and gene mutation status were set as key secondary endpoints.
Results: We identified 88 patients with extended RAS/BRAF/PIK3CA wild-type mCRC. Those treated with CapeOX + cetuximab (n = 52) had a 61.5% RR (95% CI, 47.0-74.7%), while those treated with FOLFOX + cetuximab (n = 36) had a 66.7% RR (95% CI, 49.0-81.4%). Patients with any mutation (n = 14) had a 42.9% RR (95% CI, 17.1-71.1%). There were no significant differences between these three groups (P = 0.298). The disease control rate was 86.5% (95% CI, 74.2-94.4%) in the CapeOX + cetuximab group, and 88.9% (95% CI, 73.9-96.9%) in the FOLFOX + cetuximab group. Maximum tumor size changes were largest in patients with wild-type mCRC treated with FOLFOX + cetuximab followed by patients with wild-type mCRC treated with CapeOX + cetuximab, and then by those with any mutation (-63.2%, -52.6%, and -27.3%, respectively; P = 0.035).
Conclusions: Patients with RAS/BRAF/PIK3CA wild-type mCRC had a sufficient RR following first-line treatment with CapeOX + cetuximab. These results suggest that this combination therapy should be considered as a treatment option for patients with advanced mCRC.
Keywords: cetuximab, BRAF, CapeOX, XELOX, PIK3CA