Background:NTRK gene fusions involving either NTRK1, NTRK2 or NTRK3 are oncogenic drivers of various solid tumor types but generally at a low frequency. TRK inhibitors such as LOXO-101, entrectinib, X396, AB-106, TL118 had remarkable and durable antitumor activities in patients (pts) with TRK fusion-positive cancers, regardless of age or tumor type. We assessed the frequency of NTRK fusions across 14, 491 advanced cancers to reveal the landscape in a wide variety of subtypes.

Methods: A multicenter study in China was initiated from July 2013, and advanced cancer patients have been enrolled as of September 2018. We analyzed data from 14, 491 clinical advanced cancer cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient.

Results: Of this entire cohort [6837 lung cancer (47.18%), 1894 breast cancer (13.07%), 1325 colorectal cancer (9.14%), 312 soft tissue sarcoma (2.15%), 260 head and neck cancer (1.79%) and 1804 others (12.45%)], 40 patients were identified with NTRK fusions, including TPM3-NTRK1, LMNA-NTRK1, IRF2BP2-NTRK1, TPR-NTRK1, SQSTM1-NTRK1, C1orf111-NTRK1, NTRK1-CUL3, LIPI-NTRK1, NTRK1-C1orf61, TARDBP-NTRK1, LOC643387-NTRK1, NFASC-NTRK1, RFWD2-NTRK1, MSN-NTRK2, ATL2-NTRK2, AGTPBP1-NTRK2, ZCCHC7-NTRK2, CALR-NTRK2, ESRP1-NTRK2, ETV6-NTRK3. NTRK fusions were seen in 0.26% (18/6837) of lung cancer [C1orf111-NTRK1+TPM3-NTRK1(1), TPR-NTRK1(1), TPM3-NTRK1(2), SQSTM1-NTRK1+NTRK1-CUL3(1), LIPI-NTRK1(1), NTRK1-C1orf61(1), LMNA-NTRK1(1), MSN-NTRK2(1), TARDBP-NTRK1+LOC643387-NTRK1(1), IRF2BP2-NTRK1(1), ATL2-NTRK2 (1), NFASC-NTRK1(1), AGTPBP1-NTRK2(1), RFWD2-NTRK1(1), ZCCHC7-NTRK2(1), CALR-NTRK2(1) and ESRP1-NTRK2]; 0.21%(4/1894) of breast cancer [ETV6-NTRK3(4)]; 0.37%(5/1325) of colorectal cancer [TPM3-NTRK1(1), ETV6-NTRK3(4)]; 3.53%(11/312) of soft tissue sarcoma [LMNA-NTRK1(3), TPM3-NTRK1(1), ETV6-NTRK3(7)]; 0.38%(1/260) of head and neck cancer [ETV6-NTRK3(1)] and 0.05%(1/1804) of others [ETV6-NTRK3(1)].

Conclusion:NTRK fusions are a rare molecular subtype in Chinese solid tumors. The NTRK gene fusions more commonly occurred in NSCLC (0.3%), CRC (0.4%) and BC (0.2%), and may occur without other targetable alterations such as EGFR, ALK, ROS1. The clinical evidence for responsiveness of NTRK fusions driven solid tumors provides an opportunity to personalize treatments and improve clinical outcomes for patients (pts).

Citation Format: Wen-xian Wang, Chun-wei Xu, Lei Lei, Xiao-jia Wang, You-cai Zhu, Yong Fang, Xiu-yu Cai, Rong-bo Lin, Li Lin, Hong Wang, Mei-yu Fang, Yin-bin Zhang, Shi-jie Lan, Xin Cai, Xin Liu, Xing-xiang Pu, Zong-yang Yu, Bing Wan, Jin-luan Li, Xian-bin Liang, Li-ping Wang, Wu Zhuang, Zi-yan Yang, Gang Chen, Tang-feng Lv, Yong Song. Large-scale study of NTRK fusions in Chinese solid tumors and using next generation sequencing: A multicenter study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 38.