The trial’s fourth preplanned interim analysis suggested that the differences in outcomes between groups would not become statistically significant, so the data safety monitoring committee recommended early reporting of the findings, according to Dr. Gralow.
At the time of analysis, the median follow-up was 5.4 years. Fifty-nine percent of the patients studied were postmenopausal at baseline.
The rate of 5-year disease-free survival, the trial’s primary endpoint, was 88% overall, with no significant difference across the three arms. Findings were the same in subgroups having different tumor types (hormone receptor positive, HER2 positive, and triple negative) and in different age groups (younger than 60 and older than 60). Five-year overall survival was 93% and likewise statistically indistinguishable across arms.
Roughly 8%-10% of patients in each arm had grade 3 or 4 toxicities. Pain was more commonly reported in the zoledronic acid and ibandronate arms, and gastrointestinal issues were more commonly reported with clodronate and ibandronate. Patients in the zoledronic acid arm had a higher rate of osteonecrosis of the jaw.
The arms were statistically indistinguishable with respect to rates of both all fractures and traumatic fractures, reported Dr. Gralow.
Overall, 76% of patients expressed a preference for oral agents at baseline as did 75% at the completion of therapy, although there was some switching between preference.