Clinical trial NCT06849362: Multicenter Retrospective Study on Optimizing Combination Immunotherapy Strategies in MSS/MSI-L/pMMR Advanced Colorectal Cancer
Official title: A Multicenter Retrospective Study on Optimizing Combination Immunotherapy Strategies for MSS/MSI-L/pMMR Advanced Colorectal Cancer: Comprehensive Clinical and Prognostic Analysis
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Metastatic Colorectal Cancer (CRC)
MSS Metastatic Colorectal Cancer
Immunotherapy
Keywords: MSS Colorectal Cancer
MSI-L Colorectal Cancer
pMMR Colorectal Cancer
Combination Immunotherapy
Lead sponsor: Central South University
Sponsor class: OTHER
First posted: 2025-02-27
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study includes patients diagnosed with microsatellite stable (MSS), microsatellite instability-low (MSI-L), or mismatch repair-proficient (pMMR) metastatic colorectal cancer (CRC) who have undergone immunotherapy-based treatment. Eligible participants are those who received immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy and/or bevacizumab as part of their treatment regimen.

Patients were enrolled from multiple medical centers, with data collected retrospectively. Inclusion criteria require a confirmed pathological diagnosis of MSS/MSI-L/pMMR CRC, available treatment and follow-up data, and a history of receiving at least one immunotherapy-based regimen. Exclusion criteria include patients lacking complete clinical records, follow-up data, or radiographic response assessments.

Brief summary: This multicenter retrospective study aims to evaluate and optimize combination immunotherapy strategies for patients with microsatellite stable (MSS), microsatellite instability-low (MSI-L), or mismatch repair-proficient (pMMR) advanced colorectal cancer (CRC). The study will analyze clinical outcomes, treatment responses, and prognostic factors in patients who received various immunotherapy regimens. Data from multiple institutions will be collected to identify potential predictive biomarkers and effective therapeutic combinations. The findings may provide critical insights for improving immunotherapy strategies in MSS/MSI-L/pMMR CRC patients.

Detailed description: This multicenter retrospective cohort study aims to evaluate the effectiveness of combination immunotherapy strategies in microsatellite stable (MSS), microsatellite instability-low (MSI-L), and mismatch repair-proficient (pMMR) advanced colorectal cancer (CRC) patients. Given the limited response of these CRC subtypes to immune checkpoint inhibitors (ICIs) alone, this study seeks to identify optimal combination regimens that can enhance therapeutic efficacy.

Study Objectives:

1. To assess clinical outcomes (e.g., overall survival, progression-free survival, objective response rate) in patients receiving different immunotherapy combinations.
2. To evaluate predictive biomarkers that may influence treatment response in MSS/MSI-L/pMMR CRC.
3. To compare the efficacy of various immunotherapy-based regimens, including ICIs combined with chemotherapy, targeted therapy, or anti-angiogenic agents like bevacizumab.

Methods:

* Data Source: Patient records from multiple institutions will be retrospectively analyzed.
* Patient Population: Individuals diagnosed with MSS/MSI-L/pMMR advanced CRC who have received at least one line of immunotherapy-based combination treatment.
* Data Collection: Demographics, tumor characteristics, treatment regimens, survival outcomes, and biomarker profiles.
* Statistical Analysis: Kaplan-Meier survival analysis, Cox proportional hazards model, and subgroup analyses based on biomarker expression.

Eligibility Criteria:

Approval was obtained from the institutional review boards of all four centers, adhering to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and reported in accordance with the STROCSS 2024 criteria. Informed consent was not required.

* Inclusion Criteria:

  * Patients with MSS metastatic colorectal cancer who underwent immunotherapy.
  * Comprehensive collection of demographic and molecular characteristics.
  * Patients were included irrespective of treatment context.
* Exclusion Criteria:

  * Individuals lacking definitive pathological diagnosis.
  * Patients without response evaluation data.
  * Cases missing pertinent follow-up information.

Treatment Response Evaluation:

Treatment responses were evaluated radiographically according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 guidelines.

Ethical Considerations:

Ethical approval was obtained from the institutional ethics committee of our hospital, ensuring compliance with ethical and regulatory standards for retrospective studies.

Expected Outcomes:

The study aims to identify effective treatment strategies for MSS/MSI-L/pMMR CRC patients, provide real-world evidence on the role of combination immunotherapy, and explore potential predictive biomarkers to improve patient selection for immunotherapy-based approaches.

This research will contribute to optimizing treatment strategies for immunotherapy-resistant CRC subtypes and guide future clinical trials.

Eligibility criteria: Inclusion Criteria:1) study subjects were mCRC patients with explicitly stated MSS/MSI-L/pMMR status; 2) at least one cohort included immunotherapy treatment; 3); primary outcomes of this study were defined as Disease Control Rate (DCR) and Progression-Free Survival (PFS); secondary outcomes included Objective Response Rate (ORR), Overall Survival (OS), and Adverse Drug Reactions (ADRs) Exclusion Criteria: individuals lacking definitive pathological diagnosis, response evaluation, or pertinent follow-up data

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Primary outcomes:
measure: Disease Control Rate
timeFrame: 02/28/2024
measure: Progression-Free Survival
timeFrame: 02/28/2024
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 02/28/2024
measure: Overall Survival
timeFrame: 02/28/2024
Other outcomes:
Locations:
city: Changsha
country: China
facility: Xiangya hospital, CSU
state: Hunan
Study officials:
References: