Phase 3 trial of hypofractionated versus conventionally fractionated postmastectomy RT with IMN irradiation for high-risk breast cancer

When coverage of internal mammary nodes (IMN) is required, the efficacy and safety of hypofractionated regimens within postmastectomy radiotherapy (PMRT) remain to be established. The noninferiority phase 3 HypoMast-IMNI trial at Fudan University (Shanghai, China) evaluated hypofractionated radiotherapy (HypoRT) in patients with high-risk, operable breast cancer undergoing PMRT with IMN irradiation (IMNI). Patients with high-risk disease after mastectomy (pT1-4N2-3, pT3-4N1, or pT1-2N1 with additional high-risk factors) were randomized 1:1 to HypoRT (42.56 Gy in 16 fractions; n=747) or conventionally radiotherapy (ConvRT; 50 Gy in 25 fractions; n=747). The primary endpoint was locoregional recurrence (LRR). After a median follow-up of 58.1 months in the modified intention-to-treat population (n=1429), the 5-year cumulative incidence of LRR was 1.7% with HypoRT and 2.2% with ConvRT, meeting the noninferiority criterion (p=0.017). No significant differences were observed in 5-year distant metastasis-free survival, breast cancer recurrence-free survival, disease-free survival, or overall survival. Grade 3 acute skin toxicity was significantly lowere with HypoRT (1.7% versus 12.2%; p<0.001) The incidence of grade ≥ 2 radiation pneumonitis and pulmonary fibrosis was low and comparable between arms, with no ischemic cardiac events recorded. The authors conclude that for patients with high-risk operable breast cancer requiring PMRT with IMNI, the 16-fraction HypoRT regmine is noninferior to ConvRT for locoregional control, offers a superior acute toxicity profile, and demonstrates excellent pulmonary safety.