ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report,
typically based on the primary end point, may be published when key planned co-primary or
secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate
additional results from studies, published in JCO or elsewhere, for which the primary end point has
already been reported.
The primary joint efficacy analysis of the Anthracyclines in Early Breast Cancer (ABC) trials
reported in 2017 failed to demonstrate nonanthracycline adjuvant therapy was noninferior to
anthracycline-based regimens in high-risk, early breast cancer. Full analyses of the studies
had proceeded when the prespecified futility boundary was crossed at a planned futility analysis
for the ability to demonstrate noninferiority of a nonanthracycline regimen with continued
follow-up. These results were presented with 3.3 years of median follow-up. This manuscript
reports results of the final analyses of the study efficacy end points conducted with 6.9 years of
median follow-up. Long-termanalysis of invasive disease-free survival (IDFS), the primary end
point of the ABC trials, remains consistent with the original results, as noninferiority of the
nonanthracycline regimens could not be declared on the basis of the original criteria. The
secondary end point of recurrence-free interval, which excluded deaths not due to breast cancer
as events, favored anthracycline-based regimens, and tests for heterogeneity were significant
for hormone receptor status (P 5 .02) favoring anthracycline regimens for the hormone
receptor–negative cohorts. There was no difference in overall survival, and review of the type of
IDFS events in the groups suggested reductions in cancer recurrences achieved with anthracycline
regimens were offset by late leukemias and deaths unrelated to breast cancer.