The mCRC Patients With pMMR/MSS or dMMR/MSI-H Status Received Palliative Chemotherapy Efficacy and Survival

The Metastatic Colorectal Cancer Patients With Proficient Mismatch Repair (pMMR) / Microsatellite Stable (MSS) or Deficient Mismatch Repair (dMMR) / Microsatellite Instability High (MSI-H) Status Received Palliative Chemotherapy Efficacy and Survival

Deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H) accounts for 4-5% in metastatic colorectal cancer (mCRC). The efficacy and survival of patients with dMMR/MSI-H status received palliative chemotherapy have not clear yet. In this study, the investigators observed the efficacy and survival of dMMR/MSI-H status mCRC patients received palliative first-line chemotherapy.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer Metastatic; Microsatellite Instability High; Mismatch Repair Deficiency

Detailed Description

Colorectal cancer (CRC) is the one of most common cancer in the world. Loss of function of DNA mismatch repair (MMR) is an important mechanism of CRC development. Mutation or modification of MMR genes result in MMR protein deficient (dMMR) and microsatellite instability (MSI). It has been reported that the dMMR or MSI high (MSI-H) phenotype is present in approximately 15-18% of CRC patients. Most dMMR/MSI-H tumors are sporadic CRC, and only approximately 3% of dMMR/MSI-H tumors are Lynch syndrome (LS) or hereditary nonpolyposis colorectal carcinoma (HNPCC).

The dMMR/MSI-H status was reported to be a predictive marker for adjuvant chemotherapy. Multiple retrospective studies showed that dMMR/MSI-H is correlated with a favorable prognosis in stage II/III CRC. Previous studies suggested that dMMR/MSI status may be a predictive marker of decreased benefit form adjuvant monotherapy of 5-fluorouracil (5-FU) in patients with stage II disease, but not in those with stage III disease. For metastatic colorectal cancer (mCRC), the relationship of the MMR/MSI phenotype and prognosis is unclear. Some researchers found that CRC patients with the dMMR/MSI-H phenotype have a worse prognosis. But other researchers thought the dMMR/MSI-H phenotype is no associate to efficacy and survival of palliative chemotherapy, even is benefit for efficacy and survival.Therefore, the aim of this study was to clarify whether the status of dMMR/MSI-H affected progression-free survival (PFS) in mCRC patients who received first-line palliative chemotherapy.

• Study Type: Observational
• Enrollment (Actual): 671

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The metastatic colorectal patients with different MMR or microsatellite status received palliative chemotherapy

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Histologically confirmed Metastatic colorectal adenocarcinoma;
3. Immunohistochemistry confirmed mismatch repair status or polymerase chain reaction (pCR) / next-generation sequencing (NGS) confirmed microsatellite status
4. Received palliative chemotherapy and have complete information of treatment

Exclusion Criteria:

1. Patients have not tested for mismatch repair or microsatellite
2. Patients have not received palliative chemotherapy or received palliative chemotherapy but treatment information incomplete

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
pMMR/MSS mCRC patients; The metastatic colorectal cancer patients with proficient mismatch repair or microsatellite stable status.
dMMR/MSI-H mCRC patients; The metastatic colorectal cancer patients with deficient mismatch repair or microsatellite instability high status.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	up to 24-36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	From first patient first visit to 6 month after last patient first visit
Disease Control Rate (DCR)	Based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	From first patient first visit to 6 month after last patient first visit
Overall survival	The time from registration to death due to any cause, or censored at date last known alive.	up to approximately 9 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: The Second Affiliated Hospital of Kunming Medical University
• Investigators: Principal Investigator: Ying Jin, MD.,PhD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2019
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): June 8, 2020

Study Registration Dates

• First Submitted: July 18, 2020
• First Submitted That Met QC Criteria: July 18, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 23, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Chemotherapy; Microsatellite Instability High; Colorectal Cancer Metastatic; Mismatch Repair Deficiency
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Genomic Instability; Colorectal Neoplasms; Microsatellite Instability
• Other Study ID Numbers: dMMR/MSI-H and chemotherapy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No