Clinical study of Xianjun formula combined with standard western therapy in metastatic colorectal cancer

Abstract

BACKGROUND

Colorectal cancer (CRC) represents a common malignancy for which treatment choices remain constrained with a poor prognosis in advanced stages. Immune checkpoint inhibitors (ICIs) are highly effective in microsatellite instability-high or mismatch repair-deficient CRC, but this subgroup is small. Most patients with metastatic CRC (mCRC) exhibit microsatellite-stable (MSS) or proficient mismatch repair (pMMR) status and derive minimal benefit from ICI monotherapy, largely due to an immunologically “cold” tumor microenvironment. Although combination strategies with anti-angiogenic agents, histone deacetylase inhibitors, or gut microbiota modulation have been explored, effective options remain limited for patients who have progressed after third-line or later therapies. Our preliminary studies suggest that Xianjun formula can modulate the tumor immune microenvironment and synergize with immunotherapy, offering a potential novel strategy for late-line treatment.

AIM

To evaluate overall survival (OS) in patients with MSS mCRC receiving Xianjun formula combined with standard Western therapy in the third-line or later setting, and to explore progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR).

METHODS

This multicenter, prospective, single-arm exploratory study will enroll 44 patients with MSS/pMMR mCRC who have progressed after at least three lines of therapy. Patients will receive oral Xianjun formula granules in combination with investigator-selected standard Western treatments until disease progression, unacceptable toxicity, or withdrawal. OS serves as the primary endpoint; secondary endpoints include PFS, ORR, DCR, and treatment-related adverse events graded according to CTCAE v6.0. Patients will be followed every 3 weeks, with radiologic evaluations every 2 months. Survival will be analyzed using the Kaplan-Meier method. This single-arm study is designed to generate hypotheses and inform the design of future randomized controlled trials.

RESULTS

As an exploratory study, this trial aims to preliminarily evaluate survival trends in late-line MSS mCRC patients treated with Xianjun formula combined with standard Western therapy. Improvements in OS and PFS are anticipated, along with acceptable safety profiles, providing a foundation for subsequent investigations employing larger cohorts or randomized controlled methodologies.

CONCLUSION

This prospective exploratory study is designed to provide preliminary evidence on the efficacy and safety of Xianjun formula combined with standard Western therapy in patients with heavily pretreated MSS mCRC. By targeting the immunosuppressive tumor microenvironment, this combination strategy may offer a feasible and potentially beneficial treatment option for patients who lack effective standard therapies in the late-line setting. The results of this study are expected to support further large-scale or randomized controlled trials evaluating integrative therapeutic approaches in MSS mCRC.

Keywords: Xianjun formula; Metastatic colorectal cancer; Microsatellite stable; Late-line therapy; Overall survival; Integrative medicine

Core Tip: Most metastatic colorectal cancer (mCRC) patients are microsatellite stable (MSS) and derive limited benefit from immune checkpoint inhibitor-based therapies, especially in late-line settings. This prospective, multicenter, single-arm clinical trial explores the feasibility and survival benefit of integrating Xianjun formula, a traditional Chinese medicine compound, with standard Western therapies in refractory MSS mCRC. By targeting the tumor immune microenvironment, this study aims to provide preliminary clinical evidence supporting an integrative therapeutic strategy for patients lacking effective treatment options.