SAN ANTONIO — In light of growing excitement about the ability of bisphosphonates to boost survival and bones in early breast cancer, first results from the TEAM IIB trial seem like a let-down.
"Unfortunately, we could not confirm our hypothesis that we should treat our patients with ibandronate," reported investigator Sonja Vliek, MD, from the Netherlands Cancer Institute, Amsterdam, at the San Antonio Breast Cancer Symposium (SABCS) 2016.
"There was no proof of additional benefit of ibandronate added to exemestane over 3 years; however, there was a trend toward improved disease-free survival," added her coinvestigator, Sabine Linn, MD, PhD, from the same institution.
But, despite their results, the researchers say they're encouraged by their findings, a sentiment echoed during a question period by a senior expert who called them "quite impressive" but suggested the analysis may simply be premature.
"I do beg you to continue follow-up maybe up to 6 years because these patients will likely relapse later," said Alexander Paterson, MBChB, MD, chair of the Alberta Breast Cancer Program at the Tom Baker Cancer Center and professor of medicine and oncology at the University of Calgary, Alberta, Canada.
"To me that is a trend that's really important," Dr Paterson told Medscape Medical News afterward.
Speaking at a press conference during the meeting, Dr Linn agreed. "I think this trial is in line with all other trials of adjuvant bisphosphonates in postmenopausal women," she said, referring to the meta-analysis from the Early Breast Cancer Trialists' Collaborative Group, of which Dr Paterson is a part.
Citing the fact that a substantial number of patients have not yet completed TEAMIIB trial, and that the trial may be underpowered, Dr Linn agreed "it might be that this analysis was too early, especially for this type of breast cancer, where one might need a much longer follow-up to see the true effect of adding ibandronate."
The study enrolled 1116 postmenopausal women with early, hormone receptor–positive breast cancer from 37 Dutch hospitals.
Patients were randomly assigned to receive 5 or more years of adjuvant endocrine therapy alone or in combination with 3 years of ibandronate, 50 mg once daily.
After a median follow-up of 4.6 years, the primary endpoint, 3-year disease-free survival (defined as any breast cancer recurrence, other malignant tumor, or mortality) occurred in 94.3% of the ibandronate group vs 90.8% of controls (hazard ratio [HR], 0.80), a nonsignificant difference.
There was also a nonsignificant difference in the secondary outcome of bone metastasis (1.6% vs 4.7%, respectively; HR, 0.65).
Breaking down mortality, the investigators showed that while breast cancer mortality was higher in the control group (35.4% vs 61.7%), secondary malignancies were higher in the ibandronate group (29.2% vs 19.1%).
There were more stomach and reflux-related events in the ibandronate group (8.3% vs 2.2%), and 4 patients (0.7%) developed osteonecrosis of the jaw, which resolved in all cases, said Dr Lin.
"Just looking at an early follow-up of 4 and a half years, as they did, you're going to miss a huge number of events," commented Dr Paterson. "This ER [estrogen receptor]-positive patient population tends to live a long time with hormone treatment, so they may recur 5, 10 to 15 years after starting."
But, he said, the trend is already impressive. "With twice as many deaths in the control arm, it's not going to be statistically significant yet — but it will. The mistake here, if it is a mistake, was to jump the gun with the results."
The study was funded by unrestricted research grants from Roche Netherlands and Pfizer Netherlands. Dr. Linn receives research grants from Roche Netherlands and is on the advisory board of Roche (for bevacizumab). Dr Vliek and Dr Paterson have disclosed no relevant financial relationships.
San Antonio Breast Cancer Symposium (SABCS) 2016. Abstract S6-02. Presented December 8, 2016.
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Cite this: Ibandronate Defies Bone Drug-Breast Cancer Boost -- So Far - Medscape - Dec 13, 2016.