More Evidence for Shorter Radiation Regimen in High-Risk Breast Cancer

Hypofractionated postmastectomy radiotherapy continued to provide locoregional control for patients with high-risk breast cancer, 10-year data from a phase III trial showed.

At 10 years, the cumulative locoregional recurrence rate was 10.3% with conventional fractionated radiotherapy and 12% with hypofractionated radiotherapy (HR 1.19, 95% CI 0.79-1.82), reported Guang-Yi Sun, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, at the American Society for Radiation Oncology (ASTRO) annual meeting in Boston.

In addition, severe late toxicity was uncommon with hypofractionated radiotherapy, and grade 3 adverse events were rare.

The study was also published in Lancet Oncology.

Sun noted that this trial joins HypoG-01 and Skagen trial 1 in supporting a 3-week radiotherapy schedule for patients with high-risk breast cancer requiring nodal irradiation.

Hypofractionated radiotherapy can “improve patient convenience and healthcare efficiency without compromising long-term disease control or increase late-term events,” said Sun. “Long-term results further establish hypofractionated postmastectomy radiotherapy with regional nodal irradiation as a standard of care for patients with high-risk breast cancer.”

ASTRO invited discussant Janice A. Lyons, MD, of University Hospitals Seidman Cancer Center and Case Western Reserve University in Cleveland, noted that this is “an important study that has had, and will continue to have, a profound impact on the treatment of patients with breast cancer requiring postmastectomy radiation.”

“The question becomes whether hypofractionation is appropriate for all patients undergoing postmastectomy radiation, and importantly, which fractionation schedule should be used,” she added.

She pointed out that while patients with T4 disease were eligible for enrollment, few patients in the trial, or in HypoG-01 and Skagen trial 1, presented with these tumors.

“This underrepresentation and need for dose escalation, especially in the setting of inflammatory breast cancer, requires additional research to determine the role of hypofractionation in this setting,” Lyons said. “Understanding intrinsic tumor sensitivity as we adopt these alternative fractionation schedules will be important to determine which schedule is appropriate for each individual patient.”

In explaining the rationale behind the study, Sun noted that while hypofractionated radiotherapy is well established for breast cancer, much of the mature supporting evidence comes from whole-breast irradiation after breast-conserving surgery.

Thus, the CHN HYPOPMRT trial was designed to establish the noninferiority of hypofractionated radiotherapy compared with conventional fractionated radiotherapy in patients who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumor stage T3-4 disease.

For the study’s primary outcome of 5-year cumulative incidence of locoregional recurrence, the shorter 3-week radiotherapy schedule was noninferior to the 5-week schedule (8.3% vs 8.1%; HR 1.10, 90% CI 0.72-1.69, P<0.0001).

The study enrolled 820 patients between June 2008 and June 2016 at a single academic hospital in Beijing. Participants were randomly assigned to conventional fractionated radiotherapy (50 Gy in 25 fractions over 5 weeks) or hypofractionated radiotherapy (43.5 Gy in 15 fractions over 3 weeks) to the chest wall and supraclavicular region. Median age of the cohort was 49 years, and 94% had stage III disease.

With a median follow-up of 11.5 years in the updated analysis, the 10-year rates for the following outcomes with conventional fractionated radiotherapy versus hypofractionated radiotherapy were:

• Cumulative local recurrence: 2.0% vs 3.1% (HR 1.37, 95% CI 0.57-3.25)
• Cumulative regional recurrence: 8.8% vs 9.9% (HR 1.25, 95% CI 0.81-1.93)
• Disease-free survival: 65.2% vs 69.9% (HR 0.87, 95% CI 0.69-1.10)
• Overall survival: 72.9% vs 77.5% (HR 0.82, 95% CI 0.63-1.08)

“These results provide no evidence that the shorter regimen compromised long-term survival,” Sun noted.

Regarding safety, grade 1, 2, and 3 lymphedema rates at 10 years were 21%, 5%, and 1% in the conventional arm versus 20%, 4%, and less than 1% in the hypofractionated arm.

Grade 1 lung fibrosis occurred more frequently in the hypofractionated group than in the conventional group (20% vs 12%), while other adverse events did not differ significantly between groups.

No cases of brachial plexopathy were observed during follow-up, and no serious adverse events or treatment-related deaths occurred.