18F-FDG-PET-guided, pathological complete response-adapted chemotherapy de-escalation in HER2-positive early breast cancer: 5-year outcomes and exploratory ctDNA analyses from the randomized phase 2 PHERGain trial

Authors:
Preprint
Publisher website
Google Scholar
Abstract
PHERGain is a randomized, non-comparative phase 2 trial evaluating an 18F-FDG-PET–guided, pathological complete response (pCR)-adapted strategy to omit chemotherapy in HER2-positive early breast cancer (EBC). Patients were randomized to receive chemotherapy plus trastuzumab and pertuzumab (HP; group A) or HP ± endocrine therapy (ET; group B). In group B, treatment was adapted according to PET response after two cycles and pCR, with chemotherapy administered to non-responders or patients without pCR. After a median follow-up of 5.6 years, 5-year invasive disease-free survival (iDFS) was 89.5% (95% CI, 85.7–93.4) in group B and 92.4% (95% CI, 86.7–98.5) among PET responders achieving pCR without chemotherapy, with one distant recurrence. Detectable ctDNA at baseline or during treatment was associated with inferior iDFS, whereas ctDNA clearance correlated with higher pCR rates and improved long-term outcomes. These findings continue to support the clinical validity of a PET-guided, pCR-adapted approach and suggest a potential role for ctDNA in refining treatment individualization.