Research Papers:

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

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

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Oncotarget. 2016; 7:75145-75154. https://doi.org/10.18632/oncotarget.12612

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Limin Zhang1,*, Tao Jiang1,*, Chao Zhao2,*, Wei Li1, Xuefei Li2, Sha Zhao1, Xiaozhen Liu1, Yijun Jia1, Hui Yang1, Shengxiang Ren1, Caicun Zhou1

1Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, P.R. China

2Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China

*These authors contributed equally to this work

Correspondence to:

Caicun Zhou, email: [email protected]

Shengxiang Ren, email: [email protected]

Keywords: non-small-cell lung cancer, ROS1 rearrangement, crizotinib, pemetrexed, thymidylate synthase

Received: June 30, 2016     Accepted: September 29, 2016     Published: October 12, 2016


Background: ROS1 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.

Results: A 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 methods: We 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.

Conclusions: Crizotinib 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.

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