Daily Oral Ibandronate With Adjuvant Endocrine Therapy in Postmenopausal Women With Estrogen Receptor–Positive Breast Cancer (BOOG 2006-04): Randomized Phase III TEAM-IIB Trial

Abstract

PURPOSE For postmenopausal patients with breast cancer, previous subgroup analyses have shown a modest benefit from adjuvant bisphosphonate treatment. However, the efficacy of oral nitrogen-containing bisphosphonates such as ibandronate is unclear in this setting. TEAM-IIB investigates adjuvant ibandronate in postmenopausal women with estrogen receptor–positive (ER+) breast cancer. METHODS TEAM-IIB is a randomized, open-label, multicenter phase III study. Postmenopausal women with stage I-III ER+ breast cancer and an indication for adjuvant endocrine therapy (ET) were randomly assigned 1:1 to 5 years of ET with or without oral ibandronate 50 mg once daily for 3 years. Major ineligibility criteria were bilateral breast cancer, active gastroesophageal problems, and health conditions that might interfere with study treatment. Primary end point was disease-free survival (DFS), analyzed in the intention-to-treat population. RESULTS Between February 1, 2007, and May 27, 2014, 1,116 patients were enrolled, 565 to ET with ibandronate (ibandronate arm) and 551 to ET alone (control arm). Median follow-up was 8.5 years. DFS was not significantly different between the ibandronate and control arms (HR 0.97; 95% CI, 0.76 to 1.24; log-rank P = .811). Three years after random assignment, DFS was 94% in the ibandronate arm and 91% in the control arm. Five years after random assignment, this was 89% and 86%, respectively. In the ibandronate arm, 97/565 (17%) of patients stopped ibandronate early because of adverse events. Significantly more patients experienced GI issues, mainly dyspepsia, in the ibandronate arm than in the control arm (89 [16%] and 54 [10%], respectively; P < .003). Eleven patients in the ibandronate arm developed osteonecrosis of the jaw. CONCLUSION In postmenopausal women with ER+ breast cancer, adjuvant ibandronate 50 mg once daily does not improve DFS and should not be recommended as part of standard treatment regimens.

UpToDate®

“…No benefit with adjuvant ibandronate in postmenopausal women with breast cancer (September 2022) For postmenopausal women with at least a moderate risk of breast cancer recurrence, adjuvant bisphosphonates have improved disease-free survival (DFS) outcomes in randomized trials. However, in a new randomized trial in over 1100 postmenopausal women, oral ibandronate 50 mg daily did not improve DFS relative to placebo [1,2]. Although a previous head-to-head trial that included both pre-and postmenopausal women found similar DFS outcomes with clodronate, ibandronate, and zoledronic acid, this trial is now the second in postmenopausal women to fail to show a DFS benefit from ibandronate over placebo.…”

Clinical practice guidelines for full‐cycle standardized management of bone health in breast cancer patients

“…Clinical studies of adjuvant bisphosphonates and other bone‐modifying agents to prevent bone metastasis and improve overall survival in early breast cancer are shown in Table 3 [15, 49–55].…”

“…[15,[49][50][51][52][53][54][55].2.2.2.3 | Recommendationsa. Population: Adjuvant bisphosphonates therapy should be considered in all postmenopausal (natural or treatment-induced) patients with primary breast cancer, regardless of HR and human epidermal growth factor receptor 2 (HER2) status[56].…”

Joint report SIPMO-SIOMMMS sulla MRONJ in pazienti in cura con antiriassorbitivi per prevenire la CTIBL

“…Più numerosi casi di MRONJ furono riportati in studi con farmaci AR nel setting "adiuvante", con valori tra lo 0,3% e il 5%, ma con schedule diverse e dosi più alte di quelle utilizzate nei pazienti trattati per CTIBL [18][19][20][21][22][23][24][25] .…”