Randomized phase II study of zoledronate dosing every four versus eight weeks in patients with bone metastasis from lung cancer (Hanshin Cancer Group0312)

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2023-08, Vol.182, p.107261-107261, Article 107261
• Main Authors: Katakami, Nobuyuki, Nishimura, Takashi, Hidaka, Yu, Hata, Akito, Nishino, Kazumi, Mori, Masahide, Hirashima, Tomonori, Takase, Naoto, Kaneda, Toshihiko, Ohnishi, Hisashi, Morita, Satoshi, Hatachi, Yukimasa
• Format: Article
• Language: English
• Subjects: Bone metastasis; Bone Neoplasms - drug therapy; Bone Neoplasms - secondary; Diphosphonates - therapeutic use; Dosing schedule; Every four vs eight weeks; Humans; Imidazoles - adverse effects; Lung cancer; Lung Neoplasms - drug therapy; Randomized phase 2; Zoledronate; Zoledronic Acid - therapeutic use
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2023.107261

•Patients with bone metastases from lung cancer.•4 mg of zoledronate every four weeks (4wk-ZA) or every eight weeks (8wk-ZA).•Primary endpoint; time to first skeletal related event (SRE), its rate and types.•SREs; pathologic bone fracture, bone radiation or surgery, spinal cord compression.•ZA every eight weeks did not result in an increased risk of SREs over one year. Zoledronic acid (ZA) reduces the incidence of skeletal-related events (SREs) in patients with bone metastases from solid tumors. However, the optimal dosing interval of ZA for patients with lung cancer is uncertain. We conducted a randomized, open-label, feasibility phase 2 trial at eight Japanese hospitals. Patients with bone metastases from lung cancer were randomly assigned to receive either 4 mg of ZA every four weeks (4wk-ZA) or every eight weeks (8wk-ZA). The primary endpoint was the time to the first SRE and the rate and types of SREs after one year. SREs were defined as pathologic bone fracture, bone radiation therapy or surgery, and spinal cord compression. Secondary endpoints were the SRE incidence at six months, pain assessment, changes in analgesic consumption, serum N-telopeptide, toxicity, and overall survival. Between November 2012 and October 2018, 109 patients were randomly assigned to the 4wk-ZA group (54 patients) and the 8wk-ZA group (55 patients). The number of patients who received chemotherapy or molecular-targeted agents was 30 and 23 and 18 and 16 in the 4wk-ZA and 8wk-ZA groups, respectively. The median time to the first SRE could not be calculated because of a low SRE. The time to the first SRE of all patients did not differ between the groups (P = 0.715, HR = 1.18, 95% CI = 0.48, 2.9). The SRE rate of all patients after 12 months was 17.6% (95% CI = 8.4, 30.9%) in the 4wk-ZA and 23.3% (95% CI = 11.8, 38.6%) in the 8wk-ZA group, without significant differences between the groups. There was no difference in any secondary endpoint between groups, and these endpoints did not differ among treatment modalities. An eight-week ZA interval does not increase the SRE risk for patients with bone metastasis from lung cancer and could be considered clinically.