A hypofractionated radiotherapy regimen was noninferior to conventional radiotherapy for locoregional control among patients with high-risk breast cancer undergoing postmastectomy radiotherapy with internal mammary node irradiation, according to findings from the phase III HypoMast-IMNI trial reported by Wang et al in the Journal of Clinical Oncology. The shorter hypofractionated regimen was also associated with significantly less severe acute skin toxicity, without an increase in cardiopulmonary toxicity.
Study Details
The prospective, randomized, open-label, noninferiority trial enrolled women aged 18 to 70 years who had undergone mastectomy with negative margins and axillary lymph node dissection for high-risk invasive breast cancer. Eligible patients had pathologic T1-4N2-3 or T3-4N1 disease, or T1-2N1 disease with additional high-risk features, including young age (< 40 years), grade 3 histology, lymphovascular invasion, hormone receptor negativity, or HER2 overexpression. Patients who had received neoadjuvant chemotherapy were excluded.
Between September 2018 and July 2022, 1,494 patients were randomly assigned to receive hypofractionated radiotherapy (42.56 Gy in 16 fractions) or conventionally fractionated radiotherapy (50 Gy in 25 fractions). Both regimens targeted the chest wall and regional lymph nodes, including the internal mammary nodes. Most patients received intensity-modulated radiotherapy. The primary endpoint was locoregional recurrence; secondary endpoints included distant metastasis–free survival, breast cancer recurrence–free survival, disease-free survival, overall survival, and treatment-related toxicity.
Key Results
After exclusions, the modified intention-to-treat population included 1,429 patients (716 in the hypofractionated radiotherapy group and 713 in the conventional radiotherapy group). At a median follow-up of 58.1 months (range = 15.0–84.7 months), 11 locoregional recurrences occurred with hypofractionated radiotherapy vs 15 with conventional radiotherapy. The 5-year cumulative incidence of locoregional recurrence was 1.7% vs 2.2%, respectively (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.32–1.51), meeting the prespecified noninferiority criterion (P = .017).
No significant differences were observed in secondary survival outcomes. Five-year distant metastasis–free survival was 92.3% with hypofractionated radiotherapy vs 92.7% with conventional radiotherapy (HR = 1.00, 95% CI = 0.68–1.47; P = .987). Corresponding rates were 91.8% vs 92.3% for breast cancer recurrence–free survival, 88.5% vs 89.4% for disease-free survival, and 95.1% vs 96.1% for overall survival.
Hypofractionated radiotherapy was associated with significantly less grade 3 acute skin toxicity (1.7% vs 12.2%; P < .001). Rates of grade 1 to 2 skin pruritus (26.7% vs 35.2%; P = .001) and skin pain (7.7% vs 23.3%; P < .001) were also lower.
Cardiopulmonary toxicity was comparable between groups. Grade 2 or higher radiation pneumonitis occurred in 2.0% vs 2.1% of patients, respectively, and grade 2 pulmonary fibrosis occurred in 1.3% of both groups. No ischemic cardiac events, grade 4 toxicities, or treatment-related deaths were reported.
“For patients with high-risk, operable breast cancer requiring [postmastectomy radiotherapy] with [internal mammary node irradiation], the 16-fraction [hypofractionated radiotherapy] regimen is noninferior to [conventionally fractionated radiotherapy] for locoregional control, offers a superior acute toxicity profile, and demonstrates excellent cardiopulmonary safety,” the investigators concluded.
Jinli Ma, MD, PhD, of the Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; the Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; and Clinical Research Center for Radiation Oncology, Shanghai Key Laboratory of Radiation Oncology, Shanghai, China, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the Noncommunicable Chronic Diseases–National Science and Technology Major Project, and others. For full disclosures of the study authors, visit ascopubs.org.
