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

Frontiers in Oncology

Oncology

Min Jin¹  Min Wu²  Jun Shi³  Francesco Puccetti⁴  Xue-Wei Dong⁵  Zhao-Ji Guo⁶  Qing-Qing Ding⁷  Robert L. Coleman⁸  Su-Fen Liu⁹  Mehmet Akce^1,10  Jun-Jing Zhou^1,11  Wen-Feng Lu^1,12  Li-Chao Xu^1,13  Xiao-Dong Jiao^1,14  Miao-Miao Wang^1,14  Yan Ling^1,14  Yuan-Sheng Zang^1,14  Ling-Yan Yuan^1,14  Zhan Wang^1,14  Bao-Dong Qin^1,14  Ying Wu^1,14  Ke Liu^1,14  Wen-Xing Qin^1,14  Wen-Yu Zhu^1,15  Xue-Qin Chen^1,16  Hong Shen^1,17  Ting Li^1,18  Hao Li^1,19  Yi Zhong^2,20  Hui Yang^2,21  Chérif Akladios^2,22  Yu Zeng^2,23  Kimberley Mak^2,24  Wei Jia^2,25  Savio George Barreto^2,26  Yuan-Yuan Xu^2,27  Shi-Hua Yao^2,28  Pei-Juan Zhou^2,29  Anthony W. Kim^3,30  Xiao-Ming Qiu^3,31 

[1] Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Gastrointestinal Surgery, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China;Department of Gastrointestinal Surgery, San Raffaele Hospital IRCCS, Milan, Italy;Department of Gastrointestinal Surgery, The First People’s Hospital of Changzhou, Soochow University, Changzhou, China;Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China;Department of Geriatric Oncology, Jiangsu Provincial People’s Hospital, Nanjing Medical University, Nanjing, China;Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Gynecology, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China;Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, United States;Department of Hepatobiliary and Pancreatic Surgery, Wuxi No.4 People’s Hospital, Jiangnan University, Wuxi, China;Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China;Department of Interventional Radiology, Shanghai Cancer Center, Fudan University, Shanghai, China;Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China;Department of Medical Oncology, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China;Department of Medical Oncology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China;Department of Medical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China;Department of Medical Oncology, Shanghai Cancer Center, Fudan University Shanghai Cancer Center, Shanghai, China;Department of Medical Oncology, Shanghai Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China;Department of Medical Oncology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;Department of Medical Oncology, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China;Department of Obstetrics and Gynecology, University of Strasbourg, Strasbourg, France;Department of Pathology, Shanghai Tongji Hospital, Shanghai Tongji University, Shanghai, China;Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA, United States;Department of Respiratory, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia;Department of Surgical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China;Department of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China;Department of Traditional Chinese Medicine, Shanghai Renji Hospital, Shanghai Jiaotong University, Shanghai, China;Division of Thoracic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States;Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China;

关键词: intractable cancer;    basket trial;    targeted therapy;    gene alteration;    precision medicine;   

DOI  :  10.3389/fonc.2023.860711

 received in 2022-01-23, accepted in 2023-02-02,  发布年份 2023

来源: Frontiers

【 摘 要 】

PurposeWe 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 methodsThe 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.ResultsIn 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%).ConclusionThe 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.

【 授权许可】

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Copyright © 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