# PERSEPHONE

Source: https://onco.cc/trials/persephone/  
OnCo record `persephone` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Six months of trastuzumab was almost as good as twelve, with half the heart toxicity, though twelve remains the global standard.

## Summary

PERSEPHONE, trial NCT00712140 sponsored by Cancer Research UK and reported in 2019, showed that six months of adjuvant trastuzumab for HER2-positive early breast cancer was almost as good as twelve, with half the heart toxicity, though twelve months remains the global standard. It randomised 4,088 women and met its non-inferiority endpoint on four-year disease-free survival, with cardiac events requiring discontinuation in four percent against eight percent. OnCo links it to trastuzumab, the trastuzumab cardiotoxicity term, Helena Earl, Judith M. Bliss, Andrew Wardley, the bottleneck of wrong doses and the idea of funding trials of shorter courses of expensive adjuvant drugs. The other shorter-duration trials PHARE, SOLD and Short-HER did not establish non-inferiority, so most guidelines retain twelve months while accepting six where resources are limited.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT00712140
- Phase: 3
- Setting: Adjuvant HER2+ early breast cancer: 6 vs 12 months of trastuzumab
- Sponsor: Cancer Research UK
- Enrolled: 4088
- Result: 4-year DFS 89.4% vs 89.8%, non-inferior.
- Outcomes: 4-year disease-free survival: 6 months trastuzumab 89.4% vs 12 months trastuzumab 89.8%, HR 1.07
- Replication: PHARE, SOLD, Short-HER did not establish non-inferiority; pooled analyses suggest a small loss with shorter therapy in higher-risk disease.

## Sources

- ClinicalTrials.gov NCT00712140: https://clinicaltrials.gov/study/NCT00712140

## Connected records

- cancers: [Early HER2-positive breast cancer](https://onco.cc/cancers/her2-positive-early-breast-cancer/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/)
- technologies: [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- drugs: [Trastuzumab](https://onco.cc/drugs/trastuzumab/)
- terms: [Estimands and intercurrent events (ICH E9(R1))](https://onco.cc/terms/estimand/), [Intention-to-treat (ITT) and per-protocol analysis](https://onco.cc/terms/intention-to-treat/), [Non-inferiority margin and equivalence trials](https://onco.cc/terms/non-inferiority-margin/), [Non-inferiority trial](https://onco.cc/terms/non-inferiority/), [Trastuzumab cardiotoxicity](https://onco.cc/terms/trastuzumab-cardiotoxicity/)
- people: [Andrew Wardley](https://onco.cc/people/andrew-wardley/), [Helena Earl](https://onco.cc/people/helena-earl/), [Judith M. Bliss](https://onco.cc/people/judith-bliss/)
- key papers: [6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial](https://onco.cc/key-papers/paper-persephone-lancet-2019/)
- institutions: [Cancer Research UK](https://onco.cc/institutions/cruk/)
- bottlenecks: [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- ideas: [Fund trials that test shorter courses of the most expensive adjuvant drugs](https://onco.cc/ideas/idea-cost-shorter-course-trials/)
- roadmaps: [Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation](https://onco.cc/roadmaps/global-access-roadmap/), [Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on](https://onco.cc/roadmaps/trial-modernisation-roadmap/)

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