TOPLINE

At 10 years of follow-up, the landmark FAST-Forward trial confirmed that a 1-week radiotherapy regimen of 26 Gy in five fractions provided durable cancer control and similar long-term toxicity compared with the standard 3-week schedule in patients with early-stage breast cancer, supporting its continued use as a standard of care.

METHODOLOGY

• The FAST-Forward trial was designed to determine whether an ultrahypofractionated schedule — 26 Gy or 27 Gy in five fractions over 1 week — could safely replace the standard 40 Gy in 15 fractions over 3 weeks following surgery in patients with early-stage breast cancer.
• Previous 5-year results established noninferiority of the 26 Gy regimen and led to widespread adoption of this 1-week schedule. But because disease recurrence and late normal tissue effects can emerge years after treatment, investigators also planned a 10-year follow-up analysis.
• The multicenter, open-label, phase 3 noninferiority trial enrolled 4110 patients at 97 hospitals in the UK between 2011 and 2014. After 23 withdrew consent, 4087 were included in the intention-to-treat analysis and randomly assigned to receive 40 Gy in 15 fractions over 3 weeks, 27 Gy in five fractions over 1 week, or 26 Gy in five fractions over 1 week to the breast or chest wall following breast-conserving surgery or mastectomy.
• The primary endpoint was ipsilateral breast tumor recurrence, with the current analysis reporting the prespecified 10-year outcomes.
• A subsequent randomized substudy enrolled 469 patients requiring axillary nodal radiotherapy to evaluate whether the shorter regimens were similarly effective and safe when regional lymph nodes were included in the radiation field.

TAKEAWAY

• At 10 years, the 26 Gy regimen remained noninferior to standard radiotherapy. The cumulative incidence of ipsilateral breast recurrence was 2.1% vs 3.6% with 26 Gy in five fractions vs 40 Gy in 15 fractions (absolute difference, -1.2%; hazard ratio [HR], 0.66; 95% CI, 0.41-1.04).
• Long-term normal tissue effects were similar between the 26 Gy and standard regimens. At the 10-year assessment, moderate or marked clinician-reported breast or chest wall effects were reported in 14.4% vs 13.1% of patients receiving 26 Gy vs standard radiotherapy.
• The 27 Gy regimen produced similar tumor control (10-year ipsilateral breast recurrence, 2.9% vs 3.6% with standard therapy) but higher rates of late normal tissue effects, with moderate or marked breast or chest wall effects reported in 19.3% receiving 27 Gy vs 14.4% receiving 26 Gy.
• In the nodal irradiation substudy, locoregional recurrence at 5 years was similar with 26 Gy and standard treatment (4.2% vs 4.1%), and pooled analyses showed results consistent with the main trial for both efficacy and late normal tissue effects, supporting the use of the 1-week regimen in patients requiring axillary radiotherapy.

IN PRACTICE

“Long-term follow-up confirms that 26 Gy in five fractions over 1 week is safe and efficacious for adjuvant radiotherapy to the breast or chest wall, supporting its use as a standard of care,” the study authors concluded.

SOURCE

The study, led by Adrian Murray Brunt, University of Keele, Keele, and The Institute of Cancer Research, London, England, was published online in The Lancet Oncology.

LIMITATIONS

Some subgroups were small and underpowered to show differences between schedules, although subgroup analyses demonstrated consistency of effects and adequately powered trials of less common subgroups are not likely to be feasible. Both clinician-reported and patient-reported 10-year normal tissue effect data are incomplete due to dropout and missed assessments, with patients with missing data tending to have higher grade disease and be more likely to have comorbidities, although the extent of missing data was similar across treatment groups. For less common late events such as cardiac events or second cancers, sample size and extent of follow-up would not be sufficient to show differences between schedules, and only the first occurrence of a second cancer was recorded. The nodal substudy was not powered for efficacy outcomes, resulting in relatively wide CIs that reflect the smaller cohort size, which limits the precision of efficacy estimates for this subgroup alone.

DISCLOSURES

The study received support from the National Institute for Health and Care Research Health Technology Assessment Programme and Cancer Research UK. Judith Bliss disclosed receiving research grants from Novartis (previously GSK), AstraZeneca, Janssen-Cilag, Merck Sharp & Dohme, Puma Biotechnology, Pfizer, Eli Lilly and Company, and others outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.