Primary resistance to immunotherapy in patients with a dMMR/MSI metastatic gastrointestinal cancer: who is at risk? An AGEO real-world study
Menée à partir de données portant sur 399 patients atteints d'un cancer gastro-intestinal avec déficience du système de réparation MMR et instabilité des microsatellites, cette étude identifie des facteurs cliniques associés à la résistance primaire aux inhibiteurs de points de contrôle immunitaires
Background : The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization.
Methods : This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022.
Results : 399 patients were included, 284 with colorectal cancer (CRC) and 115 with non-CRC, mostly treated by an anti-PD(L)1 (88.0%). PFS at 24 months was 55.8% (95CI [50.8–61.2]) and OS at 48 months was 59.1% (95CI [53.0–65.9]). ORR was 51.0%, and 25.1% of patients were ICIPR. There was no statistical difference in ORR, DCR, PFS, or OS between CRC and non-CRC groups. In multivariable analysis, ICIPR was associated with ECOG-PS
≥
2 (OR = 3.36), liver metastases (OR = 2.19), peritoneal metastases (OR = 2.00),
≥
1 previous line of treatment (OR = 1.83), and age
≤
50 years old (OR = 1.76).
Conclusion : These five clinical factors associated with primary resistance to ICIs should be considered by physicians to guide treatment choice in GI dMMR/MSI metastatic cancer patients.
British Journal of Cancer , résumé, 2023