medwireNews: A phase 3 trial has demonstrated the noninferiority of two five-fraction adjuvant radiotherapy schedules delivered over a week to the standard 15-fraction schedule given over 3 weeks for early-stage breast cancer with regard to local control.
The five-fraction regimen delivering 26 Gy of radiation, but not the one delivering 27 Gy, was also comparable to the standard of care in terms of normal tissue effects.
The researchers note that “[b]eyond its safety and effectiveness, the 26 Gy FAST-Forward schedule is convenient and substantially less expensive for patients and for health services.”
And they say: “The consistency of FAST-Forward results with earlier hypofractionation trials supports the adoption of 26 Gy in five daily fractions as a new standard for women with operable breast cancer requiring adjuvant radiotherapy to partial or whole breast.”
Writing in a commentary accompanying the research published in The Lancet, Antonin Levy and Sofia Rivera (both from Institut Gustave-Roussy in Villejuif, France) say that they “concur with the authors that 26 Gy in five fractions over 1 week might be changing practice for low-risk patients with breast cancer who have had surgery, but long-term disease outcomes and subset analyses are eagerly awaited.”
In the trial, individuals who underwent breast-conserving surgery or mastectomy for invasive breast carcinoma (pT1–3, pN0–1, M0) were randomly assigned to receive hypofractionated radiotherapy to the whole breast or chest wall at doses of 26 or 27 Gy in five fractions over 1 week or 40 Gy in 15 fractions over a 3-week period.
After a median 71.5 months of follow-up, the cumulative incidence of ipsilateral breast tumor relapse at 5 years was 1.4% for the 1368 patients in the 26 Gy group, 1.7% for the 1367 patients in the 27 Gy group, and 2.1% for the 1361 patients in the 40 Gy group. This equated to an absolute difference of –0.7% and –0.3% for the 26 and 27 Gy treatment arms, respectively, versus the control 40 Gy arm.
“The upper confidence limits excluded an increase in ipsilateral breast tumour relapse of 1.6% or more so noninferiority can be claimed for both five-fraction schedules compared with 40 Gy in 15 fractions,” say Adrian Murray Brunt (The Institute of Cancer Research, Sutton, UK) and fellow investigators.
Other outcomes, including locoregional and distant relapse as well as disease-free and overall survival, were also comparable between the two five-fraction schedules and the control schedule.
At the 5-year mark, moderate or marked normal tissue effects as assessed by clinicians occurred in 11.9% of patients in the 26 Gy group, 15.4% of those in the 27 Gy group, and 9.9% of those in the 40 Gy group, where the difference between the 27 and 40 Gy schedules was significant.
Longitudinal analysis of such adverse events also showed significant differences between the 27 and 40 Gy groups, but not between the 26 and 47 Gy groups, with similar findings for all but one of the individual events.
The incidence of breast appearance changes and of increased hardness or firmness of the breast as judged by patients over the follow-up period was significantly higher with the 27 versus 40 Gy schedule, but the groups were comparable in terms of changes in breast size and skin appearance. And there were no significant differences between the 26 and 40 Gy groups for any of these patient-reported outcomes.
Further highlighting the benefits of the shorter schedules, the commentators say: “During the coronavirus disease 2019 (COVID-19) pandemic, hypofractionation could restrict the exposure of health-care professionals and patients to COVID-19.
“In this context, a schedule of 26 Gy in five fractions has been endorsed by an international panel of experts.”
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Lancet 2020; doi:10.1016/S0140-6736(20)30932-6
Lancet 2020; doi:10.1016/S0140-6736(20)30978-8