Impact on survival of severe immuno-related adverse events in deficient mismatch repair/microsatellite instable-high digestive cancers treated with immunotherapy.
Severe treatment side effects don't predict better outcomes in immunotherapy-sensitive colon cancers, challenging assumptions that discomfort equals effectiveness.
In the largest study of irAEs in dMMR/MSI-H digestive cancers (n=1,175, 34 international centers), severe irAEs were associated with higher objective response rates but were not independently linked to improved PFS or OS in both time-dependent Cox and landmark analyses. These findings critically challenge the clinical assumption that irAEs serve as a biomarker of treatment benefit in this highly ICI-sensitive tumor type.
What the study was
- Study design
- International multicenter ambispective cohort study (n=1,175 from 34 centers)
- Population
- dMMR/MSI-H digestive cancer patients treated with immune checkpoint inhibitors (n=1,175; 82.9% colorectal cancer)
- Sample size
- 1175
- Category
- Treatment Innovation
- Maturity
- Potentially Practice-Changing
- Journal
- Journal for immunotherapy of cancer
Why it surfaced
Largest international multicenter study (n=1,175, 34 centers) definitively answering whether severe irAEs predict survival benefit in dMMR/MSI-H cancers treated with ICI. Negative result is practice-informing: oncologists should not use irSAE occurrence as surrogate for treatment efficacy or withhold corticosteroids to preserve 'immunity signal.'
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