Clinical benefit of zoledronic acid in patients with lung cancer and other solid tumors: Analysis based on prior history of skeletal complications

Purpose: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer. Patients and Methods: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE. Results: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P = .127 and P = .023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P = .023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P = .017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting. Conclusion: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.

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Venous Thromboembolism and Non-Small Cell Lung Cancer: A Pooled Analysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Trials.

Blood ◽

10.1182/blood.v110.11.3995.3995 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3995-3995

Author(s):

Lisa Hicks ◽

Matthew Cheung ◽

Baktiar Hasan ◽

Keyue Ding ◽

Lesley Seymour ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Adjuvant Chemotherapy ◽

Advanced Nsclc ◽

Randomized Study ◽

Pooled Analysis ◽

Small Cell ◽

Prior History ◽

Small Cell Lung ◽

History Of

Abstract Purpose: To determine the incidence of venous thromboembolism (VTE) in patients with early and advanced non-small cell lung cancer (NSCLC); to explore predictive factors for VTE occurrence during trials in these populations, and to investigate the effect of VTE on overall survival in patients with NSCLC. Patients and Methods: Data from three National Cancer Institute of Canada Clinical Trials Group trials were included in the analyses (n=1987). JBR.10 was a randomized study of post-resection adjuvant vinorelbine/cisplatin versus observation in stage IB/II NSCLC. BR.18 was a randomized study of paclitaxel/carboplatin ± the metalloproteinase inhibitor BMS-275291 in advanced NSCLC (1st line). BR.21 was a randomized study of erlotinib versus placebo in previously treated (2nd or 3rd line) NSCLC. The relationship between VTE, cancer treatment, concomitant medications, and baseline patient characteristics was explored with univariate and multivariate analysis. Cox regression analysis was performed to determine whether VTE was independently associated with survival. Each trial was analyzed separately; in addition a pooled analysis was performed with the advanced disease trials (BR.18 and BR.21). Results: The incidence of VTE was 0% in the observation arm of JBR.10 and ranged from 3% in the adjuvant chemotherapy arm of JBR.10 to 8% in BR.18. In JBR.10, VTE was independently associated with the administration of adjuvant chemotherapy (p=0.015), baseline obesity (p=.001), and low platelet count (p=.007). For patients with advanced NSCLC, VTE was significantly more common in patients receiving chemotherapy (BR.18) compared to patients receiving erlotinib or placebo (BR.21) (8% vs 2%, p< 0.0001). In BR.18, but not BR.21, VTE was associated with a prior history of VTE (p=0.001). When BR.18 and BR.21 were pooled, prior VTE remained significant. In BR.18 and BR.21, VTE was associated with shorter survival in multivariate analysis (HR=1.69, 95%CI 1.32–2.17, p<.0001); further analyses, including JBR.10, are planned to explore this finding. Conclusion: VTE is a frequent event in patients with advanced NSCLC and is associated with the administration of chemotherapy. Treatment with metalloproteinase or epidermal growth factor inhibitors does not appear to increase the risk of VTE. In early NSCLC, adjuvant chemotherapy, morbid obesity and a prior history of VTE are associated with increased risk. VTE is associated with shortened survival in patients with advanced NSCLC. Funding for this study was provided by the Canadian Cancer Society.

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