5-year results of hypofractionated locoregional radiotherapy in early breast cancer HypoG-01 (UNICANCER): a French multicentre, randomised, non-inferiority, phase 3, open-label, controlled trial.

[BACKGROUND] Hypofractionated radiotherapy is standard for whole-breast radiotherapy, but 50 Gy in 25 fractions (5-week radiotherapy) is still standard in many countries when nodal radiotherapy is needed for morbidity concerns. The UNICANCER HypoG-01 trial aimed to assess morbidity and efficacy of hypofractionated locoregional radiotherapy delivering 40 Gy in 15 fractions (3-week radiotherapy) versus 5-week radiotherapy.

[METHODS] This non-inferiority, open-label, multicentre, randomised phase 3 trial, conducted in 29 centres in France, included female patients 18 years and older, with invasive breast carcinoma requiring nodal irradiation after complete microscopic resection of the primary tumour. Patients were randomly allocated in a 1:1 ratio to either 3-week radiotherapy (experimental group) or 5-week radiotherapy (control group) to the regional nodes and thoracic wall or breast. The primary endpoint was ipsilateral arm lymphoedema, defined as a 10% or greater increase in arm circumference at 15 cm proximal, 10 cm distal, or both, to the ipsilateral olecranon relative to baseline and contralateral arm, with a non-inferiority margin on the hazard ratio (HR) of 1·545. This trial was registered at ClinicalTrials.gov (NCT03127995) and is closed to recruitment.

[FINDINGS] Between Sept 26, 2016, and March 27, 2020, 1265 patients were enrolled, and 1221 were included in per-protocol analysis (median follow-up 4·8 years [IQR 4·01-5·02]), 614 assigned to 3-week radiotherapy and 607 to 5-week radiotherapy. The median age was 58 years (IQR 49-68). Arm lymphoedema occurred in 275 (25%) patients (143 with 3-week radiotherapy and 132 with 5-week radiotherapy). 3-week radiotherapy was non-inferior to 5-week radiotherapy regarding arm lymphoedema risk (HR 1·02 [95% CI 0·79-1·31] p<0·001), with a 3-year cumulative incidence of 23·4% (95% CI 19·7-27·6) and 22·2% (95% CI 19·5-26·3), respectively. Safety profiles were similar between groups; grade 3 or worse adverse events frequencies were 8% and 13%, respectively. Following French regulation, data on race and ethnicity were not collected.

[INTERPRETATION] 3-week radiotherapy (40 Gy in 15 fractions) was found to be non-inferior to 5-week radiotherapy (50 Gy in 25 fractions) for arm lymphoedema risk and was comparably safe regarding other late normal tissue effects for patients prescribed locoregional radiotherapy for early-breast cancer.

[FUNDING] French National Cancer Institute.