# Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial (TRIUMPH)

Source: https://onco.cc/key-papers/paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021/  
OnCo record `paper-nakamura-triumph-ctdna-pertuzumab-trastuzumab-her2-colorectal-nat-med-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first trial to let a blood test decide who joins: patients whose plasma showed extra HER2 responded to dual HER2 antibodies just as often as those selected on tissue, while a matched group on standard salvage therapy had no responses at all.

## Summary

TRIUMPH was a phase 2 trial of pertuzumab plus trastuzumab in metastatic colorectal cancer with HER2 amplification confirmed prospectively by tumour tissue or ctDNA analysis. HER2 amplification was confirmed in tissue or ctDNA in 30 patients. The study met its primary endpoint with a confirmed objective response rate of 30% in 27 tissue-positive patients and 28% in 25 ctDNA-positive patients, against 0% in a matched real-world reference population treated with standard-of-care salvage therapy. Post hoc analyses showed that baseline ctDNA genotyping of HER2 copy number and concurrent oncogenic alterations, adjusted for tumour fraction, stratified patients by efficacy with accuracy similar to tissue genotyping, and that a decrease in ctDNA fraction three weeks after starting treatment was associated with response.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Nature Medicine
- Year: 2021
- DOI: 10.1038/s41591-021-01553-w
- Authors: Nakamura Y, Okamoto W, Kato T, et al.
- Findings: Confirmed objective response 30% in 27 tissue-positive and 28% in 25 ctDNA-positive patients, against 0% in matched real-world salvage therapy.; Plasma HER2 copy number adjusted for tumour fraction stratified efficacy as well as tissue did.; Falling ctDNA fraction at three weeks tracked response.
- What it means: It is the proof that plasma genotyping can enrol patients for a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.
- Caveats: 30 patients, single arm, with a real-world rather than randomised comparator.; Concurrent RAS alterations in plasma predicted poor response, so a HER2 call alone is not enough.; Plasma sensitivity depends on tumour fraction, so negative plasma does not exclude amplification.

## Sources

- Nakamura et al., Nat Med 2021: TRIUMPH, ctDNA-guided pertuzumab plus trastuzumab in HER2-amplified metastatic colorectal cancer: https://doi.org/10.1038/s41591-021-01553-w
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34764486/

## Connected records

- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/), [HER2 ISH amplified (ERBB2 gene amplification)](https://onco.cc/biomarkers/her2-ish-amplified/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [HER2](https://onco.cc/targets/her2/)
- drugs: [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Gene amplification and copy-number change](https://onco.cc/terms/gene-amplification/)
- trials: [CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)](https://onco.cc/trials/circulate-japan/)
- people: [Takayuki Yoshino](https://onco.cc/people/yoshino-takayuki/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)

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