HER2-PET imaging to predict trastuzumab deruxtecan (T-DXd) efficacy in advanced breast cancer: The phase II PREDICT-HER trial

PREDICT-HER

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with advanced breast cancer starting trastuzumab deruxtecan, a negative HER2-PET scan predicted no objective response with a negative predictive value of 88.2%, meeting the prespecified threshold.

N

89Patienten

Design

Single-arm, non-randomised phase II trial in 89 patients with advanced breast cancer due to start trastuzumab deruxtecan (HR-positive HER2-low or HER2-zero patients had progressed on a prior CDK4/6 inhibitor). Before treatment, all had baseline 18F-FDG PET/CT and HER2-PET/CT with 18F- or 68Ga-labelled affibody molecules, and were classed as HER2-PET-positive or HER2-PET-negative by visual assessment.

Endpunkt

Negative predictive value of HER2-PET-negative status for objective response to trastuzumab deruxtecan, tested against a threshold of at least 85%.

ErgebnisNegative predictive value of HER2-PET-negative status for objective response 88.2% (15/17), meeting the primary endpoint. It was 100% (10/10) in HER2-low/zero patients. Median PFS 13.6 vs 5.1 months in HER2-PET-positive (n=72) vs HER2-PET-negative (n=17) patients (multivariable-adjusted HR 0.11, 95% CI 0.05-0.26). Positive predictive value of HER2-PET-positive status in HER2-positive patients 93.8% (15/16). Normalised HER2 SUVmax 8.1 in responders vs 3.9 in non-responders (P < 0.001).

Jin J, Li P, Li T, et al. Presented at ESMO Congress 2026, abstract LBA17, 24 October. Not yet published.

Diskussion & Kritik

In this single-arm phase II trial, a negative HER2-PET scan met its prespecified negative predictive value threshold for no response to trastuzumab deruxtecan. However, the estimate rests on only 17 PET-negative patients, and the abstract gives no confidence interval for it. The large PFS difference comes from a non-randomised comparison of unequal groups, with follow-up not stated, so it may partly reflect prognosis rather than benefit from the drug. It does not show that withholding treatment from PET-negative patients improves outcomes. These are initial results: the abstract reports no reader agreement for the visual scan reads, no comparison between the two tracers and no safety data.