Article Abstract

Zoledronic acid as potential efficacy application combined with icotinib for non-small cell lung cancer with bone metastases

Authors: Wenxian Wang, Zhengbo Song, Yiping Zhang


Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now widely used to treat EGFR mutated non-small cell lung cancer (NSCLC), with icotinib being one such EGFRTKI. The incidence of bone metastases ranges from 30% to 40 % in patients with NSCLC. Zoledronic acid is a third-generation bisphosphonate. Some reports have described the possibility of direct and indirect antitumor effects of zoledronic acid.
Methods: We retrospectively evaluated survival data of 171 patients who received icotinib with progression-free survival (PFS) more than 6 months and received zoledronic acid at least once from July 2011 to May 2015 in Zhejiang cancer hospital. And we analyzed PFS and overall survival (OS) by the Kaplan-Meier method. Multivariate regression was assessed by the Cox proportional hazards model.
Results: We enrolled 171 NSCLC patients with bone metastases were treated with zoledronic acid and icotinib. A total of 133 (77.8%) patients were with EGFR-mutated (72 with deletions in exon 19, 59 with L858R mutation in exon 21 and 2 with G719X mutation in exon 18). Median Progression free survival (mPFS) of all patients during icotinib treatment was 11.0 months. And median overall survival (mOS) was 24.6 months. PFS in group of ≥1 year, between 1 year and 6 months group, and group of <6 months Zoledronic acid (ZOL) treatment were 11.7, 10.9 and 9.6 months respectively (P=0.224). For mOS, in the three groups were 24.6, 24.4 and 23.0 months (P=0.217). In 133 EGFR mutated patients, mPFS in three groups were 12.7, 11.0 and 10.6 months respectively (P=0.203). And the mPFS in ≥1 year and <6 months ZOL group were 12.7 months and 10.6 months (P=0.055).
Conclusions: Hence, combining EGFR-TKIs with zoledronic acid may have potential anticancer application for NSCLC with bone metastases and inhibit TKI resistance, particularly in EGFR mutated patients.