A large randomized trial showed that three different bisphosphonates have similar efficacy in early-stage breast cancer.
A large randomized trial showed that three different bisphosphonates have similar efficacy in early-stage breast cancer. The results of the phase III SWOG/Alliance/ECOG-ACRIN/NCIC Clinical Trials Group/NRG Oncology S0307 study (abstract 503) were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.
The trial randomized 6,097 women with stage I to III breast cancer to one of three adjuvant bisphosphonate therapy arms for 3 years: oral clodronate at 1,600 mg once daily, oral ibandronate at 50 mg once daily, or intravenous zoledronic acid at 4 mg once a month for 6 months and then every 3 months. All patients underwent surgery prior to starting adjuvant therapy.
According to the study presenter, Julie Gralow, MD, of the University of Washington in Seattle, the trial had aimed to enroll 5,400 patients but resulted in a final accrual of more than 6,000.
The primary endpoint of 5-year disease-free survival was about 88% across all three therapy arms (P = .71). Overall survival was 93% in all three arms.
The frequency of fractures was the same in all three treatment arms. About three-quarters of patients preferred taking an oral pill rather than the intravenous injection.
At the fourth interim analysis in September 2014, with 56% of the expected events, the data safety monitoring committee concluded that, with longer follow-up, the event rate was not likely to be significantly different between the three treatment arms.
There were no differences in outcomes based on patient age or menopause status. Patients had a median age of 53 years, and 58% were postmenopausal or were older than age 50. Seventy-seven percent of patients had estrogen receptor–positive disease, 17% had HER2-positive disease, and 16% had triple-negative disease. Forty-nine percent of patients were lymph node–positive.
Though bisphosphonates are typically prescribed to slow bone loss, this trial tested whether they have anti-cancer activity. There is preclinical evidence of anti-tumor activity in human cell lines and animal models, including synergistic activity with chemotherapy agents.
The three different drugs had similar safety profiles. Patients in the ibandronate arm had slightly higher grade 3/4 adverse events (10.5%) compared with patients in the clodronate arm (8.3%) and zoledronic acid arm (8.8%). Rates of osteonecrosis of the jaw were statistically significantly higher in the zoledronic acid arm (1.27%) compared with the clodronate arm (0.31%) and the ibandronate arm (0.71%) (P = .003).
Further studies are needed to understand whether bisphosphonates have anti-cancer activity since this study’s design did not include a placebo comparator arm.