The study aims to explore the clinical utility of circulating tumour DNA (ctDNA) in assessing for alterations of anti-epidermal growth factor receptor (EGFR) primary resistance in RAS and BRAF wild-type metastatic colorectal cancer (CRC) patients treated with anti-EGFR monoclonal antibodies (cetuximab / panitumumab) in combination with fluorouracil (FU)-doublet chemotherapy.

A single blood sample (20mL) will be collected after the patient has given informed consent. The blood sample will be collected within 4 weeks prior to the patient starting chemotherapy. Blood samples collected will be processed in accordance with the Guardant360 Clinical Blood Collection Kit instructions (Guardant Health, Inc.).

Patient outcomes with respect to response rate, progression-free survival, overall survival, toxicities and other co-morbid conditions will be ascertained by medical record review conducted by the study personnel. Prospective clinical data that will be collected include: patient demographics, tumor stage and pathological tumor characteristics at diagnosis, laboratory data at diagnosis and serial pre-specified time points, imaging outcomes, chemotherapy information, date of recurrence, and date and cause of death.

Although the data will be censored at the study end-points, the patient's medical record will be reviewed indefinitely to follow the health outcomes.

Inclusion Criteria:

• Patients with newly diagnosed stage IV colon or rectal cancer who are RAS/BRAF wild-type by routine tumor profiling and who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies. Prior treatment with adjuvant therapy is allowed if completed more than 6 months prior to relapse of disease.

Exclusion Criteria:

• Pregnant women will be excluded from the study.
• Patient unable to give informed consent will be excluded from the study.
• Patients who have previously received chemotherapy in the metastatic setting.
• Patients who have previously received adjuvant chemotherapy less than 6 months prior to relapse of metastatic disease.

Patients with newly diagnosed RAS/BRAF wild-type mCRC who are beginning standard-of-care treatment with fluorouracil-based doublet chemotherapy in combination with anti-EGFR monoclonal antibodies will be recruited into the study. These are patients who are cared for at the National University Cancer Institute, Singapore (NCIS), and identified through the colorectal surgery, medical oncology and multidisciplinary CRC tumour board at NCIS.