Zoledronic acid in patients with stage IIIA/B NSCLC: results of a randomized, phase III study

Ann Oncol. 2012 Aug;23(8):2082-2087. doi: 10.1093/annonc/mds128. Epub 2012 Jun 22.

Abstract

Background: Bone metastases are common in patients with advanced non-small-cell lung cancer (NSCLC) and can have devastating consequences. Preventing or delaying bone metastases may improve outcomes.

Patients and methods: This study evaluated whether zoledronic acid (ZOL) delayed disease progression or recurrence in patients with controlled stage IIIA/B NSCLC after first-line therapy. Patients received vitamin D and calcium supplementation and were randomized to i.v. ZOL (every 3-4 weeks) or no treatment (control). The primary end point was progression-free survival (PFS).

Results: No significant intergroup differences were observed in PFS or overall survival (OS). Median PFS was 9.0 months with ZOL versus 11.3 months for control. Fifteen ZOL-treated (6.6%) and 19 control patients (9.0%) developed bone metastases. Estimated 1-year OS was 81.8% for each group. ZOL safety profile was consistent with previous clinical data, but with higher discontinuations versus control. Fifteen ZOL-treated (6.6%) and five control patients (2.3%) had renal adverse events. Two cases of osteonecrosis of the jaw were reported.

Conclusions: ZOL did not significantly affect PFS or OS in stage IIIA/B NSCLC patients with controlled disease, with a trend toward worsening PFS in the longer-term follow-up. Few patients experienced bone metastases, possibly limiting the potential ZOL impact on disease course.

Trial registration: ClinicalTrials.gov NCT00172042.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / prevention & control*
  • Bone Neoplasms / secondary*
  • Calcium / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Dietary Supplements
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Imidazoles / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Vitamin D / administration & dosage
  • Young Adult
  • Zoledronic Acid

Substances

  • Diphosphonates
  • Imidazoles
  • Vitamin D
  • Zoledronic Acid
  • Calcium

Associated data

  • ClinicalTrials.gov/NCT00172042