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. 2016 Nov 15;7(46):75145-75154.
doi: 10.18632/oncotarget.12612.

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

Limin Zhang  1 , Tao Jiang  1 , Chao Zhao  2 , Wei Li  1 , Xuefei Li  2 , Sha Zhao  1 , Xiaozhen Liu  1 , Yijun Jia  1 , Hui Yang  1 , Shengxiang Ren  1 , Caicun Zhou  1
Affiliations

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

Limin Zhang et al. Oncotarget. .

Abstract

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST

None.

Figures

Figure 1
Figure 1. Flow chart of the study design
Figure 2
Figure 2
(A) Progression-free survival (PFS) of ROS1 fusion-positive patients treated with crizotinib. (B) Comparison of PFS in three major ROS1 fusion patterns-positive patients treated with crizotinib.
Figure 3
Figure 3. Progression-free survival (PFS) of ROS1 fusion-positive patients treated with cizotinib, pemetrexed-based chemotherapy and non-pemetrexed-based chemotherapy, respectively
(A) Comparison of PFS in ROS1 fusion-positive patients who received cizotinib, pemetrexed-based chemotherapy or non-pemetrexed-based chemotherapy as their any line treatment. (B) Comparison of PFS in ROS1 fusion-positive patients who received pemetrexed-based chemotherapy or non-pemetrexed-based chemotherapy as their first line treatment. (C) Comparison of PFS in ROS1 fusion-positive patients who received cizotinib, pemetrexed-based chemotherapy or non-pemetrexed-based chemotherapy as their ≥ second-line treatment.
Figure 4
Figure 4
(A) Comparison of progression-free survival (PFS) in ROS1 fusion-positive patients who received pemetrexed-based chemotherapy as 1st line or > 2nd line treatment. (B) Correlation of tumor thymidylate synthase (TS) RNA levels with PFS of ROS1 fusion-positive patients treated with pemetrexed-based chemotherapy. TS RNA levels were compared with the median TS value of control cases of NSCLC.
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