Zoledronic Acid Every 12 Weeks Is Noninferior to Every 4 Weeks for Bone Metastases

Zoledronic Acid Every 12 Weeks Is Noninferior to Every 4 Weeks for Bone Metastases

Zoledronic acid administered every 12 weeks was noninferior to an every 4-week regimen in the phase III CALGB 70604 trial of patients with breast cancer, prostate cancer, or multiple myeloma with bone metastases (Abstract 9501). Results were presented Monday, June 1, during the Patient and Survivor Care Oral Abstract Session.

Dr. Andrew Louis Himelstein

Andrew L. Himelstein, MD, FACP, of the Helen F. Graham Cancer Center & Research Institute, presented the results of the noninferiority trial that included 1,822 patients who were randomly assigned to receive zoledronic acid every 12 weeks or every 4 weeks for 2 years. The primary endpoint was incidence of any skeletal-related event (SRE); 1,766 patients were included in the primary endpoint cohort and 795 completed the 2 years of treatment.

There was no significant difference between the two arms for the primary endpoint, with 29% of patients in both the 4-week arm and the 12-week arm experiencing at least one SRE (p = 0.79). When examining patients according to disease type, there was also no significant difference between the proportion of patients with at least one SRE according to treatment arm.

No significant differences were found between the two arms for time to first SRE (p = 0.60), skeletal morbidity rate (p = 0.75), pain scores (p = 0.75), or Eastern Cooperative Oncology Group performance status (p = 0.64).

Renal dysfunction and osteonecrosis of the jaw were uncommon toxicities and did not significantly differ between the two treatment arms. However, discussant Jamie H. Von Roenn, MD, FASCO, of ASCO, said that this lack of difference was not surprising “because the bulk of toxicity from bisphosphonates is likely to occur after 2 years.”

The researchers also reviewed bone turnover markers in 2,530 samples taken from 553 patients, including C-telopeptide. Dr. Himelstein said that C-telopeptide correlates with N-telopeptide but is not as influenced by diet or time of day. The C-telopeptide assay is also less variable and more reproducible than the current N-telopeptide assay.

From weeks 12 to 36, levels of C-telopeptide were suppressed more in patients receiving zoledronic acid every 4 weeks compared with every 12 weeks (p < 0.01)

“[Although] there was a statistically significant difference between the two arms, this wasn’t clinically significant, meaning that even with lesser suppression of the bone turnover markers, our patients who took treatment every 12 weeks did no worse than those who took it every 4 weeks,” Dr. Himelstein said in a phone interview with the ASCO Daily News.

Dr. Von Roenn said that the time is right to begin recommending the use of zoledronic acid every 12 weeks instead of every 4 weeks.

“Although the economic data are not yet available, it is hard to believe that dosing a drug every 12 weeks isn’t going to be less expensive than every 4. Although, certainly, it is not going to be 3-fold less since those dosing every 3 to 4 weeks end up having treatment delays,” she said.

Watch the session: Visit the ASCO Virtual Meeting website.