This study aimis at detecting the genomic changes of ctDNA in patients of RAS and BRAF wild-type mCRC, who failed after first line treatment containing cetuximab. According to the results of ctDNA detection, individualized second-line targeted therapy strategies were developed to explore the disease control rate and prognostic significance of ctDNA-guided treatment for metastatic colorectal cancer.

Inclusion Criteria:

1. Age ≥18, gender unlimited;
2. Proven histologically by colorectal adenocarcinoma, local lesions can not be radical resection or metastatic colorectal cancer;
3. Patients with RAS and BRAF wild-type tissue genetic testing, receiving first-line treatment containing cetuximab, and radiographic evaluation of disease progression;
4. Eastern Cooperative Oncology Group (ECOG) physical condition score (PS) 0 ~ 2;
5. Expected survival of more than 3 months;
6. Within 7 days before screening (including 7 days), laboratory test data requirements were as follows: neutrophil count ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90g/L (no blood transfusion within 14 days), serum total bilirubin ≤1.25 times the upper normal limit (ULN);ALT and AST≤ 2.5 x ULN (≤5x ULN in patients with liver metastasis);Serum creatinine ≤1.0 x ULN and creatinine clearance rate ≥60 mL /min;Left ventricular ejection fraction in ultrasound examination >55%;
7. At least one measurable lesion (RECIST 1.1 criteria);
8. Subjects (or their legal representative/guardian) must sign the informed consent indicating that they understand the purpose of the study, understand the necessary procedures of the study, and are willing to participate in the study.

Exclusion Criteria:

Those who have one or more of the following will not be included in the study:

1. Have received any experimental drugs or anti-tumor drugs within 4 weeks before enrollment;
2. A history of other tumors in the past five years, except for cervix cancer or basal cell carcinoma of the skin that has been cured;
3. Patients with obvious intracranial hypertension or neuropsychiatric symptoms due to uncontrolled primary brain tumor or central nerve metastatic tumor
4. Pregnant or lactating women;Those who are fertile but do not take adequate contraceptive measures;
5. Alcoholism or drug addiction;
6. with pleural effusion or ascites, causing respiratory syndrome (≥CTCAE2 grade dyspnea), requiring local treatment;
7. Patients with the following serious or uncontrolled diseases: severe heart disease, unstable condition after treatment, myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment;Definite neuropathy or psychosis, including dementia or seizures;Severe or uncontrolled infections;Patients with active and disseminated intravascular coagulation and significant bleeding tendency
8. known hypersensitivity or anaphylaxis to any component of the study drug to be applied.
9. The function of important organs is obviously impaired
10. Other circumstances under which the investigator considers that the patient should not participate in the study

≥18y

Patients who met the entry criteria, failed after receiving first-line treatment containing cetuximab, and were judged to have progressive disease (PD) by imaging evaluation were eligible for inclusion.