SABCS: Bisphosphonate Usage Among High-Profile Clinical Trial Results

At this year’s San Antonio Breast Cancer Symposium, new data from four different clinical trials of bisphosphonate usage in patients with breast cancer will be presented and discussed.

ABCSG Trial 12

Long-term follow-up data from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 12 that is studying the effect of zoldedronic acid on outcome of estrogen-responsive early breast cancer in premenopausal women is one of the late-breaking abstracts. In 2008 the original data from this trial was reported at SABCS, showing that zoledronic acid-which is typically used for bone metastases and also osteoporosis-also benefited breast cancer patients, providing a 33% reduction in risk of breast cancer recurrence and death. It was the first trial to show this effect, but was controversial as the patient population examined was highly specific with clinicians unsure of the implications for the broad breast cancer patient population.

NSABP Protocol B-34

A second trial reporting a final analysis is the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-34. The prospective, randomized phase III trial in patients with stage I–III breast cancer looked at a 3-year oral, daily clodronate therapy compared to placebo, both in conjuction with adjuvant chemotherapy or hormone treatment. The results will show whether the 3-year regimen has an effect on survival in early-stage breast cancer patients.

ZO-FAST Trial

Yet a third trial, the ZO-FAST trial, addressed whether combination of zoledronic acid and adjuvant endocrine therapy in patients with hormone receptor–positive (HR-positive) early breast cancer is better than adjuvant therapy alone. The ZO-FAST trial data previously demonstrated that adding zoledronic acid to adjuvant therapy significantly improved bone mineral density as well as prolonged disease-free survival compared to delayed zoledronic acid treatment. The presentation this year will focus on whether patients who are diagnosed with breast cancer late after menopause receive more benefit from the combination treatment.

GAIN Study

The fourth trial is the phase III German Adjuvant Intergroup Node Positive (GAIN) study that compares breast cancer patients treated with the bisphosphonate ibandronate and one of two chemotherapy regiments for disease-free survival. The long-term follow up results of the trial will be presented.

Bisphophonates decrease skeletal pain, fractures, as well as hypercalcemia in patients with breast cancer that has metastasized to the bone. However, the role of these agents in preventing or delaying the onset of bone metastases is not clear in patients with earlier stages of breast cancer. Mixed results from previously conducted trials on oral clodronate, for example, have suggested that survival free of bone metastases is improved along with overall survival, but a third trial showed no benefit. The AZURE trial, reported last year at SABCS, reported no effect on recurrence of breast cancer and no effect on survival from zoledronic acid, though showed a potential effect on both recurrence and survival in postmenopausal women. Hopefully, the new trial data read-outs will clarify the role of bisphosphonates on improved outcomes in patients with breast cancer.

Bisphosphonate Trials at SABCS

• Long-Term Follow-Up in ABCSG-12: Significantly Improved Overall Survival with Adjuvant Zoledronic Acid in Premenopausal Patients with Endocrine-Receptor–Positive Early Breast Cancer: Abstract S1-2. Presented by Michael Gnant, MD. December 7, 2011; 9:30 a.m.

• NSABP Protocol B-34: A Clinical Trial Comparing Adjuvant Clodronate vs. Placebo in Early Stage Breast Cancer Patients Receiving Systemic Chemotherapy and/or Tamoxifen or No Therapy-Final Analysis: Abstract S2-3. Presented by Alexander H.G. Paterson, MD. December 7, 2011; 2:45 p.m.

• Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year Follow-Up of ZO-FAST: Abstract S1-3. Presented by Richard de Boer, MD. December 7, 2011; 9:45 a.m.

• GAIN Study: A Phase III Trial To Compare ETC vs. EC-TX and Ibandronate vs. Observation in Patients with Node-Positive Primary Breast Cancer-1st Interim Efficacy Analysis: Abstract S2-4. Presented by Volker Mbus, PhD. December 7, 2011; 3:00 p.m.