Efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement.

Limin Zhang,Sha Zhao,Hui Yang,Xuefei Li,Tao Jiang,Xiaozhen Liu,Wei Li,Yijun Jia,Shengxiang Ren,Caicun Zhou,Chao Zhao

doi:10.18632/oncotarget.12612

Limin Zhang, Sha Zhao + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.12612

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Journal: Oncotarget	Publication Date: Oct 12, 2016
Citations: 44	License type: cc-by

Affiliation: Shanghai Pulmonary Hospital

Abstract

BackgroundROS1 rearrangement is a novel molecular subgroup of non-small-cell lung cancer (NSCLC). This study aimed to investigate the efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement.ResultsA total of 2309 patients received ROS1 fusion detection and 51(2.2%) patients had ROS1 rearrangement. There was no significant difference between ROS1 fusion-positive and fusion-negative cohorts in demographic data. For the ROS1 fusion-positive patients, crizotinb-treated group had a higher overall response rate (ORR, 80.0%), disease control rate (DCR, 90.0%) and longer progression-free survival (PFS, 294 days) compared with the rates in pemetrexed-treated group (ORR, 40.8%; DCR, 71.4%; PFS, 179 days) and non-pemetrexed-treated group (ORR, 25.0%; DCR, 47.7%; PFS, 110 days). Besides, ORR, DCR and PFS were similar in three major ROS1 fusion partners. For the first-line treatment, patients received pemetrexed had a significant longer PFS than those received non-pemetrexed chemotherapy (209 vs. 146 days, P = 0.0107). In pemetrexed-treated cohorts, ROS1-positive patients with low TS expression had a statistically significant longer PFS than those with high TS expression (184 vs. 110 days, P = 0.0105).Materials and methodsWe retrospectively identified patients with NSCLC who were screened for ROS1 fusion using multiplex reverse transcription-polymerase chain reaction (RT-PCR) from October 2013 to February 2016. The thymidylate synthase (TS) mRNA levels were tested using quantitative real-time RT-PCR.ConclusionsCrizotinib was also highly active at treating Chinese NSCLC patients with ROS1 rearrangement. TS expression could predict the efficacy of pemetrexed-based therapy in ROS1 fusion-positive patients.

Highlights

Lung cancer is the most common malignant tumor and the leading cause of cancer death worldwide, with non-small-cell lung cancer (NSCLC) patients accounting for 80–85% of its cases [1]
There was no significant difference between ros oncogene 1 (ROS1) fusion-positive and fusion-negative cohorts in demographic data
thymidylate synthase (TS) expression could predict the efficacy of pemetrexedbased therapy in ROS1 fusion-positive patients

Summary

Introduction

Lung cancer is the most common malignant tumor and the leading cause of cancer death worldwide, with non-small-cell lung cancer (NSCLC) patients accounting for 80–85% of its cases [1]. The kinase domains of ALK and ROS1 fusion proteins display highly homology, implying that ALK-TKI, such as crizotinib, will be effective for ROS1 rearrangement-positive NSCLC patients [12]. A retrospective study showed that ROS1 fusion-positive NSCLC patients were greatly sensitive to crizotinib [14]. On the basis of the demonstration of substantial efficacy in the above phase I study, crizotinib has recently been approved by the United States Food and Drug Administration (FDA) as a treatment for patients with ROS1 fusion-positive NSCLC. The studies above were carried out among Caucasian populations It is still unknown about the efficacy of crizotinib in large-scale Chinese NSCLC patients with ROS1 rearrangement. This study aimed to investigate the efficacy of crizotinib and pemetrexed-based chemotherapy in Chinese NSCLC patients with ROS1 rearrangement

Objectives

Methods

Results