Chemotherapy Alone Versus Chemotherapy Plus Targeted Therapy as Adjuvant Therapy for Initially Unresectable Colorectal Cancer Liver Metastases

Chemotherapy Alone Versus Chemotherapy Plus Targeted Therapy as Adjuvant Therapy for Initially Unresectable Colorectal Cancer Liver Metastases: A Retrospective Cohort Study

Chemotharapy plus targeted therapy regimen, as an adjuvant therapy, can effectively reduce the rate of both intrahepatic and extrahepatic recurrence in initially unresectable CRLM patients. Those with KRAS/NRAS/BRAF mutated tumors or cycle of conversion therapy ≤ 4 can benefit more from chemotharapy plus targeted therapyrather than from chemotharapy alone, with a tolerable toxicity profile.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic
• Intervention / Treatment: Drug: Targeted agent

Detailed Description

This multi-center study enrolled consecutive patients with initially unresectable CRLM who underwent conversion therapy or radiofrequency ablation (RFA) and achieved no NED status between June 1, 2013, and June 30, 2020, from Zhongshan Hospital of Shanghai, Zhongshan Hospital of Xiamen, Cancer Hospital of Beijing. The inclusion criteria were as follows: (1) with histologically confirmed CRC; (2) with initially unresectable synchronous liver metastases (LMs); (3) accepted conversion therapy and successfully converted into resectable status; (4) underwent R0 intestinal and hepatic resection; (5) accepted adjuvant therapy. The exclusion criteria were as follows: (1) R1/R2 resection; (2) extrahepatic metastases; (3) accepted postoperative monotherapy; (4) lack of follow-up data. According to the adjuvant therapy regimen (with or without targeted therapy), the cohorts were divided into CA cohort and CT cohort. The study was approved by the ethics committee of three medical centers and was adhered to Good Clinical Practice guidelines and the Declaration of Helsinki. Written informed consent was obtained from all participants.

• Study Type: Observational
• Enrollment (Actual): 198

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Initially unresectable CRLM patients who were successfully converted and achieved no evidence of disease status from June 2013 to June 2020 were retrospectively collected. 1:2 propensity score matching (PSM) was performed to balance the baseline characteristics between CA and CT cohorts. After PSM, 196 patients werethe disease-free survival (DFS) and overall survival (OS) were evaluated between two cohorts （CA:N=66, CT:N=132）.

Description

Inclusion Criteria:

1. Age ≥ 18 and ≤ 75 years;
2. Histologically confirmed CRC;
3. Initially unresectable synchronous liver metastases (LMs);
4. Accepted conversion therapy and successfully converted into resectable status;
5. Underwent R0 intestinal and hepatic resection;
6. Accepted adjuvant therapy.

Exclusion Criteria:

1. R1/R2 resection;
2. Extrahepatic metastases;
3. Accepted postoperative monotherapy;
4. Lack of follow-up data.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chemotherapy plus Targeted therapy (CT); The treatment decisions and evaluation of treatment outcomes, such as the assessment of metastases resectability and tumor response, were carried out by the multi-disciplinary team (MDT) comprising experts from each medical centers. In this cohort, initially unresectable colorectal cancer liver metastasis (CRLM) patients who were successfully converted and achieved no evidence of disease status were treated with chemotherapy plus targeted therapy, as adjuvant therapy.	Drug: Targeted agent; The two cohorts received different adjuvant therapy regimens, with the CT group receiving chemotherapy plus targeted therapy; the CA group received chemotherapy alone.
Chemotherapy Alone (CA); In this cohort, initially unresectable colorectal cancer liver metastasis (CRLM) patients who were successfully converted and achieved no evidence of disease status were treated with chemotherapy, as adjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse-free survival	The relapse-free survival (PFS) was defined as the period from the start of initial liver resection to the date of tumor relapse or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	The overall survival (OS) was defined as the period from the start of initial liver resection until death from any cause, at which point the data was censored.	5 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jianmin Xu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2013
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: August 31, 2023
• First Posted (Actual): September 7, 2023

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: CAPTIUM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No