Age-related outcomes in MSI/dMMR gastrointestinal cancers treated by immune checkpoint inhibitors and toxicity’s impact on efficacy: an immunoMSI cohort study

Abstract

Background: Immune-checkpoint inhibitors (ICIs) are the standard of care for microsatellite instability (MSI) metastatic gastrointestinal cancer (mGIC) patients in first- and later-treatment lines. We compared tolerability and efficacy of ICIs in elderly (aged ≥75 years) versus non-elderly MSI mGIC patients and analyzed the correlation between immune-related adverse events (irAEs) and efficacy. Patients and methods: This single-center prospective cohort study included MSI mGIC patients treated with ICIs, excluding chemotherapy. Assessments covered grade ≥3 irAEs and ≥2 endocrine irAEs (E-irAEs). Results: Among 201 patients, 24 were elderly (mean age 75–90 years) and 177 non-elderly (mean age 22-74 years). In the overall population, grade ≥3 irAEs and E-irAEs incidence was 40% with the anti-programmed cell death protein 1 + anti-cytotoxic T lymphocyte-associated antigen 4 and 23% with anti-programmed cell death protein 1 monotherapy (P = 0.011). Treatment combination was administered to 29% of elderly and 40% of non-elderly patients. The incidence of grade ≥3 irAEs and E-irAEs was 37%/29% with monotherapy (P = 0.48) and 57%/39% with combination (P = 0.43) in elderly/non-elderly patients. No significant difference was observed in progression-free survival [hazard ratio (HR) = 1.15, 95% confidence interval (CI) 0.57-2.32, P = 0.7] and OS (HR = 1.61, 95% CI 0.75-3.43, P = 0.25) between elderly and non-elderly. Cox regression analysis with a time-dependent variable showed no survival difference between patients with/without grade ≥3 irAEs and E-irAEs (progression-free survival: HR = 1.19, 95% CI 0.64-2.19, P = 0.59; overall survival: HR = 0.91, 95% CI 0.44-1.92, P = 0.81). A positive association was found, however, between objective response rate and immune treatment-related adverse event occurrence [77%/59%, immune treatment-related adverse event patients/others (P = 0.0012)]. Conclusion: This study reveals comparable tolerability and efficacy of ICIs in elderly and non-elderly patients with MSI mGIC. Survival outcomes did not differ significantly between patients with and without grade ≥3 irAEs and E-irAEs.

Keywords

• immune checkpoint inhibitors
• adverse events
• microsatellite instability
• metastatic gastro-intestinal tumor
• elderly