A risk stratification model for toxicities in phase 1 immunotherapy trials
Alberto Hernando-Calvo1, Abdulazeez Salawu1, Rachel Y Chen2
1Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
European Journal of Cancer (Oxford, England : 1990)
|September 9, 2022
Summary
Novel immunotherapy agents have varying toxicity risks. A new model categorizes these risks, finding combination therapies and non-standard agents pose higher dangers. Improved trial reporting standards are essential.
Area of Science:
- Oncology
- Clinical Pharmacology
- Immunotherapy
Background:
- Novel immunotherapy (IO) agents are rapidly developing, but their toxicity profiles require further elucidation.
- Understanding IO toxicity is crucial for safe clinical trial design and patient management.
Purpose of the Study:
- To develop and apply a risk stratification model for phase 1 immunotherapy trials.
- To identify factors associated with higher toxicity risk in early-phase IO trials.
- To assess the quality of reporting in published phase 1 IO trials using established standards.
Main Methods:
- A 5-variable risk stratification model was created for IO toxicity.
- Phase 1 IO trials (Jan 2014-Dec 2020) were categorized into low-, intermediate-, and high-risk groups.
- A subset of trials was evaluated against ASCO/SITC Trial Reporting in Immuno-Oncology (TRIO) standards.
Main Results:
- Immunotherapy agents exhibited diverse risk profiles.
- Combination IO therapy and agents other than anti-PD1/L1, anti-CTLA4, or vaccines were linked to increased toxicity.
- No examined studies fully adhered to TRIO reporting standards.
Conclusions:
- The findings highlight the need for refined clinical trial designs in immunotherapy.
- Enhanced reporting standards are urgently required for immunotherapy trials to ensure clarity and consistency.
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