Prolonged survival and time to disease progression with zoledronic acid in patients with bone metastases from non-small cell lung cancer.

Abstract

e18077 Background: We previously reported that patients (pts) with bone metastases (mets) from non-small cell lung cancer (NSCLC) treated with zoledronic acid (ZOL) in addition to chemotherapy (CHT) had prolonged overall survival (OS) and time to disease progression (TTP) versus CHT alone (p < 0.01 for both; Zarogoulidis K, et al. Int J Cancer. 2009). However, the ZOL benefits reported were not adjusted for baseline covariates, and response rates at bone and primary sites were not separated. Methods: Pts with NSCLC and bone mets were assigned to treatment with CHT (docetaxel 100 mg/m2 + carboplatin AUC 6 q mo) alone if asymptomatic or CHT + ZOL (4 mg q mo) for bone pain. Disease responses (complete, partial, stable, or progressive) were assessed at bone and primary sites. The effects of treatment on OS and TTP were assessed by Cox regression in multivariate (MV) models controlling for type of bone lesions, sex, radiotherapy, and line of chemotherapy. Results: Of 144 enrolled pts, 57 received CHT alone, and 87 received CHT + ZOL. After completion of first-line CHT by all pts, the estimated rate of partial response in the primary tumor site was 2-fold higher for ZOL (32% vs 16% of pts for CHT alone), and the rate of progressive disease in bone was a relative 38% lower for ZOL (23% vs 37% of pts for CHT alone). The MV model confirmed the significantly increased median OS for CHT + ZOL vs CHT-alone pts that was detected in Kaplan-Meier (KM) analyses (median OS of 578 vs 384 d, respectively; p < 0.001). The ZOL-treated pts had a significant 39% reduced risk of death vs the CHT-alone pts (HR = 0.607; p = 0.015). Similarly, the MV model confirmed the significantly increased TTP in the CHT + ZOL vs CHT-alone pts that was detected in KM analyses (median TTP of 265 vs 150 d, respectively, p < 0.001). The ZOL-treated pts had a profound 61% reduced risk of disease progression vs the CHT-alone pts (HR = 0.392; p < 0.001). Conclusions: These analyses confirm previous results that pts with bone pain who received ZOL had superior disease progression and survival outcomes vs CHT alone in pts with asymptomatic bone mets from NSCLC. Moreover, the higher response rates in the primary tumor site with CHT + ZOL vs CHT alone suggest direct ZOL anticancer activity. No significant financial relationships to disclose.