Multicenter phase 3 trial of hypofractionated locoregional radiotherapy in early breast cancer: 5-year results of UNICANCER HypoG-01

Hypofractionated radiotherapy is standard for whole-breast radiotherapy (RT), but 50 Gy in 25 fractions (5-week RT) is still standard in many countries when nodal RT is needed for morbidity concerns. The phase 3 UNICANCER HypoG-01 trial, at 29 centers in France, compared 40 Gy in 15 fraction (3-week RT) versus 5-week RT in adult patients with early invasive breast cancer requiring nodal irradiation after complete microscopic resection of the primary tumor. Patients were randomized 1:1 to either 3-week RT (n=614) or 5-week RT (n=608) to the regional nodes and thoracic wall or breast. The primary endpoint was ipsilateral arm lymphedema, with a noninferiority margin on the HR of 1.545. 3-week RT was noninferior to 5-week RT regarding arm lymphedema risk (HR 1.02; 95% CI 0.79-1.31; p for noninferiority<0.001), with a 3-year cumulative incidence of 23.4% and 22.2%, respectively. Safety profiles were similar between groups; grade 3 or worse adverse event frequencies were 8% and 13%, respectively. The authors conclude that 3-week RT was found to be noninferior to 5-week RT for amr lymphedema risk and was comparbly safe regarding other late normal tissue effects for patients prescribed locoregional radiotherapy for early breast cancer.