As reported in The Lancet by Brunt et al, 5-year findings from the phase III FAST-Forward trial indicated that adjuvant radiotherapy with 26 Gy in 5 fractions over 1 week was noninferior to 40 Gy in 15 fractions over 3 weeks in preventing local tumor relapse in women with early-stage breast cancer.
Study Details
In the open-label multicenter trial, 4,096 patients who had undergone breast conservation surgery or mastectomy were randomly assigned between November 2011 and June 2014 to receive radiotherapy to the whole breast or the chest wall at 40 Gy in 15 fractions over 3 weeks (n = 1,361), 27 Gy in 5 fractions over 1 week (n = 1,367), or 26 Gy in 5 fractions over 1 week (n = 1,368).
The primary endpoint was ipsilateral breast tumor relapse. On the assumption of a 2% 5-year incidence of relapse with 40 Gy, noninferiority was predefined as ≤ 1.6% excess for the 5-fraction schedules (critical hazard ratio [HR] = 1.81).
Local Relapse Risk
At a median follow-up of 71.5 months, local relapse had occurred in 31 patients (2.3%) in the 40-Gy group, 27 (2.0%) in the 27-Gy group, and 21 (1.5%) in the 26-Gy group. The 5-year cumulative incidence of local relapse was 2.1%, 1.7% (HR vs 40 Gy = 0.86, 95% confidence interval [CI] = 0.51–1.44), and 1.4% (HR vs 40 Gy = 0.67, 95% CI = 0.38–1.16). The estimated absolute differences in incidence at 5 years vs 40 Gy were −0.3% for 27 Gy (P = .0022) and −0.7% for 26 Gy (P = .0002).
KEY POINTS
- Radiotherapy at 26 Gy in 5 fractions over 1 week was noninferior to 40 Gy in 15 fractions over 3 weeks in preventing local relapse.
- Rates of local relapse were 1.5% vs 2.3%.
Regional relapse occurred in 1.0%, 0.8%, and 0.7% of patients, respectively. Rates of total locoregional relapse (3.6%, 2.6%, and 2.1%), distant relapse (4.3%, 5.0%, and 5.6%), any breast cancer–related event (8.7%, 8.2%, and 8.3%), and all-cause mortality (6.8%, 7.7%, and 6.6%) were similar among groups, with no statistically significant differences observed.
Normal Tissue Adverse Effects
At 5 years, any moderate or marked clinician-assessed normal tissue adverse effects in the breast or chest wall among evaluated patients were reported in 98 (9.9%) of 986 patients in the 40-Gy group, 155 (15.4%) of 1,005 in the 27-Gy group, and 121 (11.9%) of 1,020 in the 26-Gy group. When analyzed according to total number of clinician assessments, such effects were reported in 651 (10.6%) of 6,121 patients in the 40-Gy group vs 1,004 (15.9%) of 6,303 in the 27-Gy group (odds ratio [OR] = 1.55, P < .0001) and 774 (12.2%) of 6,327 in the 26-Gy group (OR = 1.12, P = .20). Patient and photographic assessments also indicated higher normal tissue-effect risks for 27 Gy vs 40 Gy, but not for 26 Gy vs 40 Gy.
The investigators concluded, “26 Gy in 5 fractions over 1 week is noninferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumor control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.”
Adrian Murray Brunt, FRCR, of the Clinical Trials and Statistics Unit, The Institute of Cancer Research, Sutton, London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the National Institute for Health Research Health Technology Assessment Programme. For full disclosures of the study authors, visit thelancet.com.
