CALGB 70604 (Alliance): A randomized phase III study of standard dosing vs. longer interval dosing of zoledronic acid in metastatic cancer.

Patient and Survivor Care
Session Type and Session Title: 
Oral Abstract Session, Patient and Survivor Care
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr 9501)
Andrew Louis Himelstein, Rui Qin, Paul J. Novotny, Drew K. Seisler, James L. Khatcheressian, John D. Roberts, Stephen S. Grubbs, Tracey O'Connor, Douglas Weckstein, Charles L. Loprinzi, Charles L. Shapiro; Helen F. Graham Cancer Center & Research Institute, Newark, DE; Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN; Virginia Cancer Institute, Richmond, VA; Yale University, New Haven, CT; Roswell Park Cancer Institute, Buffalo, NY; New Hampshire Onc-Hem PA, Hooksett, NH; Mayo Clinic, Rochester, MN; Mount Sinai School of Medicine, New York, NY

Abstract Disclosures


Background: Zoledronic acid (ZA) given monthly for 24 months (mo) reduces bone pain and skeletal-related events (SRE) in patients (pts) with bone metastases. We tested whether ZA every 3 mo would be non-inferior to monthly for 24 mo, with less toxicity, in a randomized trial in 1822 pts: breast (n = 833), prostate (n = 674), myeloma (n = 270), and other (n = 45). Methods: SRE were defined as radiation therapy (RT) to bone, fractures, spinal cord compression or surgery to bone within 24 mo. ZA doses were adjusted for creatinine clearance. The primary endpoint was the proportion of pts in each group who had ≥ 1 SRE; secondary endpoints included skeletal morbidity rates, performance status, pain using the Brief Pain Inventory, and incidences of jaw osteonecrosis and renal dysfunction. The trial design was non-inferiority (NI) with stratification and pre-planned analyses by disease. The NI margin was 7% absolute difference. With 1,230 pts (planned sample size 1758 with 30% allowance for inevaluable pts), the power was > 82% when the NI margin was < 0 using a 1-sided test at a 5% significance level. Results: Between May 1, 2009 and April 13, 2012, 1822 pts were randomized. Baseline characteristics of the 2 groups were comparable. Dose delays were more common with ZA monthly. The 2-year cumulative incidences of SRE and selected toxicities are presented in the Table. The proportions of SRE were 29.5% vs 28.6% (95% CI for margin: -3.3% to 5.1%, Cochran-Maentel-Hanzel p = 0.79) for monthly and every 3 mo, respectively. Conclusions: ZA administered every 3 mo is non-inferior to ZA administered monthly for 24 mo in breast cancer, prostate cancer and multiple myeloma. Bone turnover markers in a subset of pts and a cost analysis will be presented. Clinical trial information: NCT00869206

Q Month
N = 911
Q 3 Months
N = 911
HR (P-value)
Total ZA dose (median)56 mg24 mg— ( < 0.01)
Dose delays62%37%— ( < 0.01)
Any SRE2602531.05 (0.60)
Any SRE – breast pts (N = 820)1131190.90 (0.43)
Any SRE – prostate pts (N = 660)1071011.15 (0.31)
Any SRE – myeloma pts (N = 265)35301.30 (0.29)
Bone RT1851631.16 (0.18)
Bone fractures62790.78 (0.13)
Spinal cord compression23300.75 (0.30)
Bone surgery22420.51 (0.01)
Jaw osteonecrosis189— (0.08)
Grade 2-4 creatinine increase115— (0.46)