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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.
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.
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a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.
Shares Gene amplification and copy-number change, HER2 ISH amplified (ERBB2 gene amplification), Receptor tyrosine kinase activation, HER2.
Shares Gene amplification and copy-number change, HER2 ISH amplified (ERBB2 gene amplification), Receptor tyrosine kinase activation, Trastuzumab.
Shares Takayuki Yoshino, CIRCULATE-Japan (GALAXY / VEGA / ALTAIR), Nature Medicine, Circulating tumour DNA (ctDNA).
Shares Cell-free DNA (cfDNA), CIRCULATE-Japan (GALAXY / VEGA / ALTAIR), ctDNA MRD positivity (molecular residual disease after curative treatment), Circulating tumour DNA (ctDNA).
Shares Pertuzumab, Circulating tumour DNA (ctDNA), Trastuzumab, HER2.
Shares Cell-free DNA (cfDNA), ctDNA MRD positivity (molecular residual disease after curative treatment), Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares Cell-free DNA (cfDNA), Guardant360 CDx, Circulating tumour DNA (ctDNA), Liquid biopsy (ctDNA).
Shares Takayuki Yoshino, ctDNA MRD positivity (molecular residual disease after curative treatment), Nature Medicine, Circulating tumour DNA (ctDNA).