The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma
The frequency and impact of ROS1 rearrangement on clinical outcomes in never smokers with lung adenocarcinoma
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DOI：
10.1093/annonc/mdt220
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发表时间：
2013-09-01
影响因子：
50.5
通讯作者：
Cho, B. C.
中科院分区：
文献类型：
--
作者：
Kim, H. R.;Lim, S. M.;Cho, B. C.
为了确定ROS 1重排的频率和对从不吸烟的肺腺癌患者治疗结果的预测影响，我们同时分析了208例从不吸烟的肺腺癌患者的ROS 1和ALK重排以及表皮生长因子受体（EGFR）和KRAS的突变。用荧光原位杂交法检测208例肿瘤中ROS 1重排7例（3.4%），ALK重排15例（7.2%）。CD 74-ROS 1融合在两名患者使用逆转录酶-聚合酶链反应。在EGFR/KRAS/ALK阴性患者中，ROS 1重排的频率为5.7%（6/105）。与未发生ROS 1/ALK重排的患者相比，发生ROS 1重排的患者对培美曲塞的客观缓解率（ORR; 60. 0% vs 8. 5%; P = 0. 01）更高，中位无进展生存期（PFS;未达到vs 3. 3个月; P = 0. 008）更长。携带ROS 1/ALK重排的患者的EGFR-酪氨酸激酶抑制剂的PFS短于不携带ROS 1/ALK重排的患者（2.5个月对7.8个月; P = 0.01）。临床选择的患者中ROS 1重排的频率高于报告的COPD患者，这表明ROS 1重排是东亚从不吸烟的肺腺癌患者的可用药靶点。考虑到与常规疗法不同的治疗结果和ROS 1抑制剂的可用性，ROS 1重排的鉴定可以导致ROS 1重排肺腺癌的成功治疗。
To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma.We concurrently analyzed ROS1 and ALK rearrangements and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization.Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase-polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01).The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.