Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid Subgroup Analysis from a Randomized Phase 3 Study
Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid Subgroup Analysis from a Randomized Phase 3 Study
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DOI：
10.1097/jto.0b013e31826aec2b
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发表时间：
2012-12-01
影响因子：
20.4
通讯作者：
Jacobs, Ira
中科院分区：
文献类型：
--
作者：
Scagliotti, Giorgio Vittorio;Hirsh, Vera;Jacobs, Ira
简介：Denosumab是一种全人源抗RANKL单克隆抗体，可降低实体瘤骨转移患者的肿瘤相关事件发生率。我们目前的生存数据的肺癌患者的子集，参加3期试验denosumab与唑来膦酸（ZA）在治疗骨转移的实体瘤（除乳腺癌或前列腺癌）或多发性myeloma.Methods：患者随机1：1每月皮下denosumab 120毫克或静脉注射ZA 4毫克。使用Kaplan-Meier估计和比例风险模型对非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）患者的总生存期进行探索性分析。结果：在811例任何肺癌患者中，与ZA相比，Denosumab与中位总生存期改善相关（8.9 vs 7.7个月;风险比[HR] 0.80）和702例NSCLC患者（9.5 vs 8.0个月; HR 0.78）（每次比较p = 0.01）。按组织学类型对NSCLC进行的进一步分析显示，在鳞状细胞癌患者中，Denosumab组的中位生存期为8.6个月，ZA组为6.4个月（HR 0.68; p = 0.035）。治疗组间总体不良事件的发生率均衡; 66.0%的地舒单抗治疗患者和72.9%的ZA治疗患者发生严重不良事件。两组间颌骨骨坏死的累积发生率相似（地舒单抗组为0.7%，ZA组为0.8%）。地舒单抗组低钙血症发生率为8.6%，ZA组为3.8%。结论：在这项探索性分析中，地舒单抗与ZA相比，可改善转移性肺癌患者的总生存率。
Introduction: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma.Methods: Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC.Results: Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA.Conclusion: In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.