Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway)

• Type of Material: Article
• Authors: Xiao-Dong Jiao, Naval Medical University, China; Bao-Dong Qin, Naval Medical University, China; Zhan Wang, Naval Medical University, China; Ke Liu, Naval Medical University, China; Ying Wu, Naval Medical University, China; Yan Ling, Naval Medical University, China; Wen-Xing Qin, Naval Medical University, China; Miao-Miao Wang, Naval Medical University, China; Ling-Yan Yuan, Naval Medical University, China; Savio George Barreto, Flinders Medical Centre; Anthony W Kim, Keck School of Medicine of the University of Southern California; Kimberly Mak, Boston University; Hao Li, Shanghai Jiao Tong University; Yuan-Yuan Xu, Shanghai Jiao Tong University; Xiao-Ming Qiu, Sichuan University; Min Wu, Huazhong University of Science & Technology; Min Jin, Huazhong University of Science & Technology; Li-Chao Xu, Fudan University; Yi Zhong, Shanghai University of Traditional Chinese Medicine; Hui Yang, Nanjing Medical University; Xue-Qin Chen, Zhejiang University School of Medicine; Yu Zeng, Shanghai Tongji University; Jun Shi, Nanjing Medical University; Wen-Yu Zhu, Nanjing Medical University; Qing-Qing Ding, Nanjing Medical University; Wei Jia, Shanghai University of Traditional Chinese Medicine; Su-Fen Liu, Nanjing Medical University; Jun-Jing Zhou, Jiangnan University; Hong Shen, Zhejiang University; Shi-Hua Yao, Naval Medical University; Zhao-Ji Guo, Soochow University; Ting Li, Fudan University; Pei-Juan Zhou, Shanghai Jiao Tong University; Xue-Wei Dong, Zhejiang Univ Sch Med; Wen-Feng Lu, Nanjing Medical University; Robert L Coleman, The University of Texas MD Anderson Cancer Center; Mehmet Akce, Emory University; Chérif Akladios, University of Strasbourg, Strasbourg, France; Francesco Puccetti, San Raffaele Hospital IRCCS; Yuan-Sheng Zang, Naval Medical University
• Language: English
• Date: 2023-02-23
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2023 Jiao, Qin, Wang, Liu, Wu, Ling, Qin, Wang, Yuan, Barreto, Kim, Mak, Li, Xu, Qiu, Wu, Jin, Xu, Zhong, Yang, Chen, Zeng, Shi, Zhu, Ding, Jia, Liu, Zhou, Shen, Yao, Guo, Li, Zhou, Dong, Lu, Coleman, Akce, Akladios, Puccetti and Zang
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2023.860711
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 13
• Start Page: 860711
• End Page: 860711
• Keywords: ASSOCIATION; CLINICAL-TRIALS; targeted therapy; gene alteration; Oncology; basket trial; SOLID TUMORS; BRAF; CELL LUNG-CANCER; SURVIVAL; GENOMICS; precision medicine; NCI-MATCH; Life Sciences & Biomedicine; ONCOLOGY; Science & Technology; VEMURAFENIB; intractable cancer
• Research Categories: Health Sciences, Oncology; Health Sciences, Obstetrics and Gynecology

Abstract

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.