AUTHOR=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 TITLE=Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway) JOURNAL=Frontiers in Oncology VOLUME=13 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.860711 DOI=10.3389/fonc.2023.860711 ISSN=2234-943X 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.