# 3-year invasive disease-free survival with chemotherapy de-escalation using an 18 F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial

Source: https://onco.cc/key-papers/paper-phergain-lancet-2024-update/  
OnCo record `paper-phergain-lancet-2024-update` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Later report from the PHERGain trial registered as NCT03161353, in The Lancet (2024); its title describes an updated or longer-term analysis.

## Summary

Background: PHERGain was designed to assess the feasibility, safety, and efficacy of a chemotherapy-free treatment based on a dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer (EBC). It used an 18 fluorine-fluorodeoxyglucose-PET-based, pathological complete response (pCR)-adapted strategy.

Methods: PHERGain was a randomised, open-label, phase 2 trial that took place in 45 hospitals in seven European countries. It randomly allocated patients in a 1:4 ratio with centrally confirmed, HER2-positive, stage I-IIIA invasive, operable breast cancer with at least one PET-evaluable lesion to either group A, where patients received docetaxel (75 mg/m 2, intravenous), carboplatin (area under the curve 6 mg/mL per min, intravenous), trastuzumab (600 mg fixed dose, subcutaneous), and pertuzumab (840 mg loading dose followed by 420 mg maintenance doses, intravenous; TCHP), or group B, where patients received trastuzumab and pertuzumab with or without endocrine therapy, every 3 weeks. Random allocation was stratified by hormone receptor status. Centrally reviewed PET was conducted at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results. Patients in group B who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, while PET-non-responders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve a pCR received six cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints were pCR in patients who were group B PET-responders after two treatment cycles (the results for which have been reported previously) and 3-year invasive disease-free survival (iDFS) in patients in group B. The study is registered with ClinicalTrials.gov (NCT03161353) and is ongoing.

Findings: Between June 26, 2017, and April 24, 2019, a total of 356 patients were randomly allocated (71 patients in group A and 285 patients in group B), and 63 (89%) and 267 (94%) patients proceeded to surgery in groups A and B, respectively. At this second analysis (data cutoff: Nov 4, 2022), the median duration of follow-up was 43·3 months (range 0·0-63·0). In group B, the 3-year iDFS rate was 94·8% (95% CI 91·4-97·1; p=0·001), meeting the primary endpoint. No new safety signals were identified. Treatment-related adverse events and serious adverse events (SAEs) were numerically higher in patients allocated to group A than to group B (grade ≥3 62% vs 33%; SAEs 28% vs 14%). Group B PET-responders with pCR presented the lowest incidence of treatment-related grade 3 or higher adverse events (1%) without any SAEs.

Interpretation: Among HER2-positive EBC patients, a PET-based, pCR-adapted strategy was associated with an excellent 3-year iDFS. This strategy identified about a third of patients who had HER2-positive EBC who could safely omit chemotherapy.

Funding: F Hoffmann-La Roche.

Indexed on Europe PMC as PubMed record 38582092 (DOI 10.1016/s0140-6736(24)00054-0). Its abstract cites the registry id NCT03161353, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: The Lancet
- Year: 2024
- DOI: 10.1016/s0140-6736(24)00054-0
- Authors: Pérez-García JM, Cortés J, Ruiz-Borrego M, et al.
- What it means: A second publication from the PHERGain trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; Chosen as a later report by words in its title (updated, long-term, final, overall survival or a year count), not by reading the paper.

## Sources

- Lancet 2024: https://doi.org/10.1016/s0140-6736(24)00054-0
- PubMed: https://pubmed.ncbi.nlm.nih.gov/38582092/
- Europe PMC: https://europepmc.org/article/MED/38582092
- ClinicalTrials.gov NCT03161353: https://clinicaltrials.gov/study/NCT03161353

## Connected records

- trials: [PHERGain](https://onco.cc/trials/phergain/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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