P3.02b-093 Zoledronic Acid Enhances the Effects of Icotinib on Non-Small Cell Lung Cancer Patients with Bone Metastases: Topic: EGFR Clinical

Abstract

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are widely used as molecularly targeted drugs for the treatment of non-small cell lung cancer (NSCLC), with icotinib being one such EGFR-TKI. Bone metastases occur in 30–40% of patients with advanced non-small cell lung cancer (NSCLC). Zoledronic acid is a third-generation bisphosphonate, and is effective for the reduction of the skeletal-related events (SREs). In addition, some reports have described the possibility of direct and indirect antitumor effects of zoledronic acid. However, most of these studies are preclinical research or combination with chemotherapy. We retrospectively analyzed data of 184 patients received icotinib with progression-free survival more than 6 months and used zoledronic acid at least once from July 2011 to May 2015 in Zhejiang cancer hospital. Progression free survival (PFS) and overall survival (OS) were calculated with the Kaplan-Meier method. Multivariate regression was performed using the Cox proportional hazards model. A total of 184 NSCLC patients with bone metastases were treated with zoledronic acid and icotinib. 140 (76.1%) patients were with EGFR mutations (75 with deletions within exon 19, 63 with L858R messenger mutation in exon 21 and 2 with G719X mutation in exon 18). Median PFS of all patients during icotinib treatment was 10.7 months. The median overall survival (OS) time for all patients was 24.3 months. The PFS in ≥1 year and <1 year zoledronic group were 12.1 months and 10.2 months (P=0.351). And the PFS in the group of ≥2 years ZOL was longer than the group of <2 years zoledronic treatment (12.2 versus 10.5 months, P=0.175). The cumulative incidences of bone pain had not increased during 1 year zoledronic treatment than before ZOL treatment (31.0% versus 45.1%). 39 of the 92 patients in ≥1 year zoledronic treatment (39.1%) and 24 of the 92 patients in <1 year zoledronic (26.1%) experienced SREs before zoledronic acid treatment (P = 0.059). During zoledronic acid treatment, the incidence rate of SREs in group of ≥1 year and <1 year were 17.4% (16/92) and 13.0% (12/92), respectively. Hence, combined treatment of EGFR-TKI with zoledronic acid may have a more effective for NSCLC with bone metastases, particularly in EGFR mutation patients.