Frontiers in Oncology (Feb 2023)
Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway)
- Xiao-Dong Jiao,
- Bao-Dong Qin,
- Zhan Wang,
- Ke Liu,
- Ying Wu,
- Yan Ling,
- Wen-Xing Qin,
- Miao-Miao Wang,
- Ling-Yan Yuan,
- Savio George Barreto,
- Anthony W. Kim,
- Kimberley Mak,
- Hao Li,
- Yuan-Yuan Xu,
- Xiao-Ming Qiu,
- Min Wu,
- Min Jin,
- Li-Chao Xu,
- Yi Zhong,
- Hui Yang,
- Xue-Qin Chen,
- Yu Zeng,
- Jun Shi,
- Wen-Yu Zhu,
- Qing-Qing Ding,
- Wei Jia,
- Su-Fen Liu,
- Jun-Jing Zhou,
- Hong Shen,
- Shi-Hua Yao,
- Zhao-Ji Guo,
- Ting Li,
- Pei-Juan Zhou,
- Xue-Wei Dong,
- Wen-Feng Lu,
- Robert L. Coleman,
- Mehmet Akce,
- Chérif Akladios,
- Francesco Puccetti,
- Yuan-Sheng Zang
Affiliations
- Xiao-Dong Jiao
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Bao-Dong Qin
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Zhan Wang
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Ke Liu
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Ying Wu
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Yan Ling
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Wen-Xing Qin
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Miao-Miao Wang
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Ling-Yan Yuan
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- Savio George Barreto
- Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia
- Anthony W. Kim
- Division of Thoracic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, United States
- Kimberley Mak
- Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA, United States
- Hao Li
- Department of Medical Oncology, Shanghai Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China
- Yuan-Yuan Xu
- Department of Surgical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
- Xiao-Ming Qiu
- Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- Min Wu
- Department Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Min Jin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Li-Chao Xu
- 0Department of Interventional Radiology, Shanghai Cancer Center, Fudan University, Shanghai, China
- Yi Zhong
- 1Department of Medical Oncology, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Hui Yang
- 2Department of Medical Oncology, Suzhou Municipal Hospital, Nanjing Medical University, Suzhou, China
- Xue-Qin Chen
- 3Department of Medical Oncology, Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yu Zeng
- 4Department of Pathology, Shanghai Tongji Hospital, Shanghai Tongji University, Shanghai, China
- Jun Shi
- 5Department of Gastrointestinal Surgery, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China
- Wen-Yu Zhu
- 6Department of Medical Oncology, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China
- Qing-Qing Ding
- 7Department of Geriatric Oncology, Jiangsu Provincial People’s Hospital, Nanjing Medical University, Nanjing, China
- Wei Jia
- 8Department of Respiratory, Shanghai Traditional Chinese Medicine-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Su-Fen Liu
- 9Department of Gynecology, Changzhou No.2 People’s Hospital, Nanjing Medical University, Changzhou, China
- Jun-Jing Zhou
- 0Department of Hepatobiliary and Pancreatic Surgery, Wuxi No.4 People’s Hospital, Jiangnan University, Wuxi, China
- Hong Shen
- 1Department of Medical Oncology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
- Shi-Hua Yao
- 2Department of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China
- Zhao-Ji Guo
- 3Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
- Ting Li
- 4Department of Medical Oncology, Shanghai Cancer Center, Fudan University Shanghai Cancer Center, Shanghai, China
- Pei-Juan Zhou
- 5Department of Traditional Chinese Medicine, Shanghai Renji Hospital, Shanghai Jiaotong University, Shanghai, China
- Xue-Wei Dong
- 6Department of Gastrointestinal Surgery, The First People’s Hospital of Changzhou, Soochow University, Changzhou, China
- Wen-Feng Lu
- 7Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
- Robert L. Coleman
- 8Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Mehmet Akce
- 9Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, United States
- Chérif Akladios
- 0Department of Obstetrics and Gynecology, University of Strasbourg, Strasbourg, France
- Francesco Puccetti
- 1Department of Gastrointestinal Surgery, San Raffaele Hospital IRCCS, Milan, Italy
- Yuan-Sheng Zang
- Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China
- DOI
- https://doi.org/10.3389/fonc.2023.860711
- Journal volume & issue
-
Vol. 13
Abstract
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.
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