Early toxicity of moderately hypofractionated radiation therapy in breast cancer patients receiving locoregional irradiation: First results of the UNICANCER HypoG-01 phase III trial

Purpose: To investigate early adverse events (AEs) in HypoG-01, a randomised, controlled, multicentre, non-inferiority phase 3 trial comparing toxicity and efficacy of adjuvant loco-regional moderately hypofractionated radiation therapy versus 2 Gy daily radiation therapy. Methods: Women ≥ 18 years with T1-3 N0-3 M0 breast cancer were randomised 1:1 after surgery +/- systemic therapy to receive either 40 Gy/15 fractions (3-week-RT) or 50 Gy/25 fractions (5-week-RT) +/-tumour-bed boost. AEs at baseline, end of treatment, and 6-month follow-up were graded using CTCAEV4.0, LENT/SOMA and Harris 4-point scales. Competing risk analysis for cumulative incidence of AEs, worst grade dermatitis according to risk factors, and cosmetic assessment were performed in the intention-to-treat (ITT) population. Results: From September 2016 to March 2020, 29 sites enrolled 1265 women. The ITT population included 1260 patients (3-week-RT: 631, 5-week-RT: 629). The proportion of patients with maximum grade ≥ 2 AEs were 284 (45 %) in 3-week-RT and 326 (51.8 %) in 5-week-RT. Overall, 88 (7 %) grade 3, one grade 4 and no grade 5 AEs were observed. Reported AEs were mostly dermatitis, fatigue, and pain, numerically lower in 3-week-RT than 5-week-RT. Grade ≥ 2 dermatitis was more frequent in patients receiving a tumour-bed boost or with BMI > 30 but numerically less frequent with 3-week-RT than 5-week-RT even in those subgroups. Of the 552 patients with breast-conserving surgery who completed cosmetic evaluation at M6, 88.4 % had excellent to good cosmetic results with no imbalance between groups. Conclusion: Early AEs were mild and do not raise safety concerns for 3-week-RT in women receiving nodal RT.