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A multicenter study evaluating efficacy of immune checkpoint inhibitors in advanced non-colorectal digestive cancers
Mathilde Moreau1, Emily Alouani2, Clémence Flecchia3
1Hepato-Gastroenterology Department, Poitiers University Hospital, Poitiers 86000, France.
Background:
One randomized phase III trial comparing chemotherapy (CT) with immune checkpoint inhibitors (ICI) has demonstrated significant efficacy of ICI in deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer. However, few studies have compared ICI with CT in other advanced dMMR/MSI-H digestive tumors.
Methods:
In this multicenter study, we included patients with advanced dMMR/MSI-H non-colorectal digestive tumors treated with chemotherapy and/or ICIs. Patients were divided retrospectively into two groups, a CT group and an immunotherapy (IO) group. The primary endpoint was progression-free survival (PFS). A propensity score approach using the inverse probability of treatment weighting (IPTW) method was applied to deal with potential differences between the two groups.
Results:
133 patients (45.1/27.1/27.8% with gastric/small bowel/other carcinomas) were included. The majority of patients received ICI in 1st (29.1%) or 2nd line (44.4%). The 24-month PFS rates were 7.9% in the CT group and 71.2% in the IO group. Using the IPTW method, IO treatment was associated with better PFS (HR=0.227; 95% CI 0.147-0.351; p < 0.0001). The overall response rate was 26.3% in the CT group versus 60.7% in the IO group (p < 0.001) with prolonged duration of disease control in the IO group (p < 0.001). In multivariable analysis, predictive factors of PFS for patients treated with IO were good performance status, absence of liver metastasis and prior primary tumor resection, whereas no association was found for the site of the primary tumor.
Conclusions:
In the absence of randomized trials, our study highlights the superior efficacy of ICI compared with standard-of-care therapy in patients with unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancer, regardless of tumor type, with acceptable toxicity.
Insights
Immune checkpoint inhibitors (ICI) show superior efficacy over chemotherapy in advanced deficient DNA mismatch repair system/microsatellite instability-high (dMMR/MSI-H) non-colorectal digestive cancers. This immunotherapy approach significantly improves progression-free survival and response rates compared to traditional chemotherapy.
Area of Science:
- Oncology
- Gastroenterology
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICI) are effective in dMMR/MSI-H metastatic colorectal cancer.
- Limited data exist on ICI efficacy in other advanced dMMR/MSI-H digestive tumors compared to chemotherapy (CT).
Purpose of the Study:
- To compare the efficacy of ICI versus CT in patients with advanced dMMR/MSI-H non-colorectal digestive tumors.
- To evaluate progression-free survival (PFS) as the primary endpoint.
Main Methods:
- Multicenter retrospective study including 133 patients with advanced dMMR/MSI-H non-colorectal digestive tumors.
- Patients were divided into chemotherapy (CT) and immunotherapy (IO) groups.
- Propensity score weighting (IPTW) was used to adjust for baseline differences.
Main Results:
- Immunotherapy (IO) was associated with significantly better PFS (HR=0.227, p < 0.0001) and 24-month PFS rates of 71.2% vs 7.9% for CT.
- Overall response rate was higher in the IO group (60.7%) compared to CT (26.3%, p < 0.001).
- Good performance status, absence of liver metastasis, and prior tumor resection predicted better PFS in patients treated with IO.
Conclusions:
- ICI demonstrates superior efficacy compared to standard-of-care chemotherapy in unresectable or metastatic dMMR/MSI-H non-colorectal digestive cancers.
- The benefits of ICI were observed regardless of tumor type, with acceptable toxicity.
- Further research, including randomized trials, is warranted to confirm these findings.
