What are the treatment options for a patient with sigmoid colon adenocarcinoma (Adenocarcinoma of the sigmoid colon), moderately differentiated, with regional and non-regional nodal metastases, classified as cT3N1bM1a, Stage IVA (American Joint Committee on Cancer (AJCC) 8th edition), and having wild-type KRAS (Kirsten Rat Sarcoma viral oncogene homolog)/NRAS (Neuroblastoma RAS viral oncogene homolog)/BRAF (B-Raf proto-oncogene) and proficient mismatch repair (pMMR)?

From the Guidelines

For a patient with Stage IVA sigmoid colon adenocarcinoma (cT3N1bM1a) that is moderately differentiated, KRAS/NRAS/BRAF wild-type, and proficient mismatch repair (pMMR), I recommend systemic therapy with an anti-EGFR agent plus chemotherapy as first-line treatment, specifically FOLFOX or FOLFIRI combined with cetuximab or panitumumab, as this approach offers the best chance for tumor shrinkage and potential conversion to resectable disease, which could significantly improve long-term outcomes. The patient's wild-type RAS/BRAF status makes this tumor particularly sensitive to anti-EGFR therapy, which blocks growth signals in cancer cells 1. According to the ESMO clinical practice guideline for diagnosis, treatment, and follow-up of metastatic colorectal cancer, delivering a biological therapy in combination with chemotherapy in the first-line setting is recommended, unless contraindicated, and in RAS-wt and BRAF-wt left-sided tumors, doublet chemotherapy plus an anti-EGFR mAb is the preferred option 1. Some key points to consider when selecting a treatment regimen include:

• Determining the RAS mutational status on a tumor biopsy is mandatory to guide the best treatment decision 1
• A doublet of chemotherapy (FOLFOX, FOLFIRI, CAPOX) that can be combined with an anti-VEGF or anti-EGFR mAb is recommended for first-line treatment 1
• Anti-EGFR mAbs can be combined with the doublets FOLFOX or FOLFIRI, and bevacizumab can be combined with single fluoropyrimidines, irinotecan or oxaliplatin-based doublet of chemotherapy (FOLFOX, CAPOX, FOLFIRI) or triplets (FOLOXIRI) 1 A typical regimen would be FOLFOX: oxaliplatin 85 mg/m² IV day 1, leucovorin 400 mg/m² IV day 1,5-FU 400 mg/m² IV bolus day 1, then 2400 mg/m² continuous infusion over 46 hours, plus cetuximab 500 mg/m² IV every 2 weeks, administered every 2 weeks for 3-6 months, followed by assessment of response 1. For patients with potentially resectable metastases, surgical evaluation should be considered after 2-3 months of therapy if good response is observed. The pMMR status indicates immunotherapy would not be beneficial as first-line treatment, making the combination of chemotherapy and anti-EGFR therapy the most appropriate option 1.

From the FDA Drug Label

Metastatic Colorectal Cancer (mCRC) RAS Wild-Type mCRC Vectibix is indicated for the treatment of adult patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test) metastatic colorectal cancer (mCRC) As first-line therapy in combination with FOLFOX As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy

Treatment Options:

• First-line therapy: Panitumumab in combination with FOLFOX for patients with wild-type RAS metastatic colorectal cancer (mCRC) 2.
• Monotherapy: Panitumumab as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy for patients with wild-type RAS mCRC 2. Key Considerations:
• The patient has KRAS/NRAS/BRAF wild-type and pMMR, which makes them eligible for panitumumab treatment.
• The patient's cancer is moderately differentiated and has regional & nonregional nodal metastases, which is consistent with Stage IVA (AJCC 8th edition).
• Panitumumab is indicated for the treatment of adult patients with wild-type RAS mCRC, which includes this patient's cancer type.

From the Research

Treatment Options for Sigmoid Colon Adenocarcinoma

• The patient has been diagnosed with sigmoid colon adenocarcinoma with regional and nonregional nodal metastases, moderately differentiated, cT3N1bM1a, Stage IVA (AJCC 8th edition) 3.
• The patient's tumor is KRAS/NRAS/BRAF wild-type and pMMR, which suggests that targeted therapies such as cetuximab and panitumumab may be effective in combination with chemotherapy 3.
• Systemic therapy, including cytotoxic chemotherapy, biologic therapy, and immunotherapy, is the primary treatment for unresectable metastatic colorectal cancer 3.

Potential Treatment Approaches

• Cetuximab monotherapy has been shown to be effective in a case report of a patient with advanced sigmoid colon cancer with liver metastases, resulting in improved laboratory tests and regression of liver metastases 4.
• Hepatic arterial infusion chemotherapy (HAI) may be a potential alternative treatment for patients with unresectable colorectal liver metastasis, as demonstrated in a case report of a patient with sigmoid colon cancer who achieved complete response via HAI 5.
• Combination chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) has been shown to be effective in patients with stage III colon cancer, although the patient's risk group and molecular features should be taken into account when selecting treatment 6.

Prognostic Factors

• Tumor deposits and extramural venous invasion on computed tomography (CT) have been identified as prognostic factors for disease-free survival in patients with sigmoid colon cancer, and may be used to preoperatively identify patients at high risk of recurrence 7.
• The patient's KRAS/NRAS/BRAF wild-type status and pMMR status may also be prognostic factors, although further research is needed to fully understand their impact on treatment outcomes 3, 6.