# Tolerability as a co-primary endpoint with its own label claim

Source: https://onco.cc/ideas/idea-moon-toxicity-first-endpoints/  
OnCo record `idea-moon-toxicity-first-endpoints` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

New cancer drugs should have to prove not only that they extend life but how they affect how people feel and function, with that result printed in the label like efficacy.

## Summary

Trials are powered on progression or survival; tolerability is described from clinician-graded adverse events and rarely tested as a hypothesis. The proposal is a regulatory framework in which a pre-specified patient-reported tolerability endpoint (e.g., PRO-CTCAE composite or physical function decline) can be co-primary or a formal secondary endpoint eligible for a label claim, with the analysis methods (time to deterioration, area under the curve, cumulative burden) standardised by regulators and academic groups such as SISAQOL-IMI.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- Hypothesis: Once tolerability claims are obtainable, sponsors will design better-tolerated regimens and doses; within five years a third of new approvals will carry a tolerability claim and median grade 3+ adverse event rates in pivotal trials will fall.
- Rationale: What can be claimed gets optimised. Regulators already accept PRO-based claims outside oncology; the analytic standards now exist.
- Proposed test: Regulator issues guidance and grants the first claims; track the proportion of pivotal protocols with powered tolerability endpoints and adverse event rates over five years against the preceding five.
- Maturity: early-clinical
- Actor: regulator

## Sources

- Bottleneck evidence (Toxicity and quality of life are undervalued): Di Maio et al., Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting (JCO 2015): https://doi.org/10.1200/JCO.2014.57.9334

## Connected records

- terms: [Immune-related adverse events (irAEs)](https://onco.cc/terms/irae/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- key papers: [Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials](https://onco.cc/key-papers/paper-di-maio-j-clin-oncol/)

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