Jiao Xiao-Dong, Qin Bao-Dong, Wang Zhan, Liu Ke, Wu Ying, Ling Yan, Qin Wen-Xing, Wang Miao-Miao, Yuan Ling-Yan, Barreto Savio George, Kim Anthony W, Mak Kimberley, Li Hao, Xu Yuan-Yuan, Qiu Xiao-Ming, Wu Min, Jin Min, Xu Li-Chao, Zhong Yi, Yang Hui, Chen Xue-Qin, Zeng Yu, Shi Jun, Zhu Wen-Yu, Ding Qing-Qing, Jia Wei, Liu Su-Fen, Zhou Jun-Jing, Shen Hong, Yao Shi-Hua, Guo Zhao-Ji, Li Ting, Zhou Pei-Juan, Dong Xue-Wei, Lu Wen-Feng, Coleman Robert L, Akce Mehmet, Akladios Chérif, Puccetti Francesco, Zang Yuan-Sheng
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai, China.
Department of Surgery, Flinders Medical Centre, Bedford Park, SA, Australia.
Front Oncol. 2023 Feb 23;13:860711. doi: 10.3389/fonc.2023.860711. eCollection 2023.
We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.
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.
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%).
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.
我们评估了分子导向靶向治疗对难治性癌症的效果。此外，还研究了中国人群中可靶向治疗基因改变的流行病学情况。
长征通路研究（ClinicalTrials.gov标识符：NCT03239015）是一项非随机、开放标签的II期试验，由多项篮式研究组成，旨在研究中国人群中难治性癌症的分子特征。该试验旨在：1）评估靶向治疗对难治性癌症的疗效；2）确定中国泛癌患者中二级基因改变的分子流行病学情况。
在第一阶段，确定了520例难治性泛癌患者的分子特征，其中115例患者存在二级基因改变。随后，这115例患者中有27例根据分子特征接受了靶向治疗。总体缓解率（ORR）为29.6%（8/27），疾病控制率（DCR）为44.4%（12/27）。中位缓解持续时间（DOR）为4.80个月（95%CI，3.33 - 27.2），中位无进展生存期（PFS）为4.67个月（95%CI，2.33 - 9.50）。在第二阶段，对17841例中国泛癌患者的分子流行病学研究表明，各癌症类型中二级基因改变的频率为17.7%。膀胱癌的二级改变最多（26.1%），其次是乳腺癌（22.4%）和非小细胞肺癌（NSCLC；20.2%）。
长征通路试验表明，分子导向靶向治疗对中国人群中的难治性癌症具有显著的临床益处。各癌症类型中二级基因改变的频率支持了篮式试验下分子导向靶向治疗的可行性。
