Research Papers:

Bisphosphonates enhance EGFR-TKIs efficacy in advanced NSCLC patients with EGFR activating mutation: A retrospective study

Chu-ying Huang _, Li Wang, Cheng-jun Feng, Ping Yu, Hong-xiao Cai, Wen-xiu Yao, Yong Xu, Xiao-ke Liu, Wen-jiang Zhu, Yan Wang, Jin Zhou, You Lu and Yong-sheng Wang

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Oncotarget. 2016; 7:66480-66490. https://doi.org/10.18632/oncotarget.5515

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Chu-Ying Huang1,3,*, Li Wang1,4,*, Cheng-Jun Feng1,*, Ping Yu2,*, Xiao-Hong Cai2, Wen-Xiu Yao2, Yong Xu1, Xiao-Ke Liu1, Wen-Jiang Zhu1, Yan Wang1,5, Jin Zhou2, You Lu1, Yong-Sheng Wang1

1Department of Thoracic Oncology, Cancer Center, and State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

2Department of Oncology, The Second People's Hospital of Sichuan, Chengdu, China

3Department of Medical Oncology, Enshi Tujia and Miao Autonomous Prefecture Central Hospital, Hubei Province, China

4Department of Dermatology, Enshi Tujia and Miao Autonomous Prefecture Central Hospital, Hubei Province, China

5Department of Oncology, The First People's Hospital of Longquanyi District, Chengdu, China

*These authors have contributed equally to this work

Correspondence to:

Yong-Sheng Wang, email: [email protected], [email protected]

Keywords: bisphosphonates, EGFR-TKIs, NSCLC, EGFR mutations, bone metastases

Received: April 30, 2015     Accepted: September 05, 2015     Published: November 27, 2015


Background: Bisphosphonates have exhibited anti-tumor activity in non-small cell lung cancer (NSCLC). We aimed to evaluate whether the combination of bisphosphonates with tyrosine kinase inhibitors of EGFR (EGFR-TKIs) could obtain a synergistic effect on advanced NSCLC patients with EGFR mutations.

Methods: Between January 2008 and October 2013, 114 advanced EGFR mutations NSCLC patients who received EGFR-TKIs as first-line therapy were recruited from two cancer centers. Patients were separated into EGFR-TKIs alone or EGFR-TKIs plus bisphosphonates (combination) group. Median progression free survival (mPFS), median overall survival (mOS) distributions and survival curves were analyzed.

Results: Among the 114 patients, 62 had bone metastases (19 patients treated with EGFR-TKIs, 43 patients treated with EGFR-TKIs + bisphosphonates). Median PFS and OS were significantly improved in combination group compared with EGFR-TKIs group (mPFS: 15.0 vs 7.3 months, P = 0.0017; mOS: 25.2 vs 10.4 months, P = 0.0015) in patients with bone metastases. Among the 71 patients (19 patients with bone metastases) treated with EGFR-TKIs alone, patients with bone metastases had poor survival prognosis (mPFS:7.3 vs 12.1 months, P = 0.0434; mOS:10.4 vs 22.0 months, P = 0.0036). The survival of patients with bone metastases who received EGFR-TKIs plus bisphosphonates therapy was non-inferior to patients without bone metastases treated with EGFR-TKIs alone (mPFS: 15.0 vs 12.1 months, p = 0.1871; mOS: 25.2 vs 22.0 months, p = 0.9798).

Conclusions: Concomitant use of bisphosphonates and EGFR-TKIs improves therapeutic efficacy and brings survival benefits to NSCLC patients with EGFR mutation and bone metastases.

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