Results from the phase 3 HypoG-01 trial show hypofractionated locoregional radiation therapy (RT) is non-inferior to normofractionated RT in terms of arm lymphedema risk in early breast cancer and did not lead to unfavorable study outcomes, according to results from the 2024 ESMO Congress in Barcelona, Spain, presented by Sofia Rivera, MD, PhD, Gustave Roussy, Paris, France.

“Hypofractionated RT is the standard regimen for whole breast RT, but normofractionated RT using 50 Gy/25 fr is still standard in most countries for loco-regional early breast cancer,” explained Dr Rivera.

HypoG-01, a UNICANCER, open-label, multicenter, randomized phase III trial aimed to assess the non-inferiority of hypofractionated RT with 40 Gy/15 fr (2.67 Gy/fr) vs normofractionated RT 50 Gy/25 fr (2.0 Gy/fr).

The trial enrolled patients ≥18 years of age with T1-3, N0-3, M0 breast cancer who received nodal and thoracic wall breast RT. Patients were randomized in a 1:1 ratio to receive either hypofractionated or normofractionated RT.

The primary end point was time to occurrence of arm lymphedema evaluated by one-sided logrank test in the per-protocol population with a non-inferiority hazard ratio (HR) margin of 1.545. The secondary end points included locoregional relapse-free survival (RFS), distant disease-free survival (DFS), and overall survival (OS).

Between September 2016 and March 202, 1265 patients were enrolled and randomized to hypofractionated (n = 614) or normofractionated (n = 607) RT, with 1221 making up the per-protocol population. The median age of patients was 58 years (range, 23 to 91), surgery included mastectomy (n = 501; 45%) and axillary clearance (n = 921; 82.8%) with a mean of 12 removed nodes.

With a median follow-up of 4.8 years, 275 lymphedemas occurred. Hypofractionated Rt was non-inferior to normofractionated RT regarding arm lymphedema risk (hazard ratio [HR], 1.02; 90% confidence interval [CI], 0.83 to 1.26; non-inferiority P <.001) with similar results in the intent-to-treat population (HR, 1.03; 90% CI, 0.83 to 1.27; non-inferiority P <.001).

The 5-year locoregional RFS rates were 92.7% (95% CI, 90.1% to 94.6%) in the hypofractionated RT arm vs 89.6% (95% CI, 86.6% to 92%) in the normofractionated RT arm (HR, 0.62; 95% CI, 0.38 to 1). The 5-year distant DFS rates were 91.3% (95% CI, 88.7% to 93.4%) vs 87.1% (95% CI, 83.8% to 89.7%), respectively (HR, 0.54; 95% CI, 0.31 to 0.96). The 5-year OS rates were 94% (95% CI, 91.6% to 95.7%) and 90.5% (95% CI, 87.4% to 92.8%), respectively (HR, 0.59; 95% CI, 0.37 to 0.93).

In the intent-to-treat population, 24 severe adverse events were reported, 16 in the hypofractionated RT arm and 11 in the normofractionated RT arm. Of these, 3 were deemed RT-related (1 in the hypofractionated arm and 2 in the normofractionated arm).

In conclusion, the HypoG-01 trial showed that moderately hypofractionated locoregional RT is non-inferior to normofractionated RT in terms of arm lymphedema risk in early breast cancer and did not lead to unfavorable safety, locoregional RFS, distant DFS, or OS concerns.

“This practice-changing trial supports the use of 40 Gy/15 fr for locoregional RT in early breast cancer,” Dr Rivera concluded.

Source:

Rivera S, Ghodssighassemabadi R, Brion T, et al. Locoregional hypo vs normofractionated RT in early breast cancer: 5 years results of the HypoG-01 phase III UNICANCER trial. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract 231O