Abstract 1265
Background
Targeted therapy based on a certain genetic alteration has been proven to be an effective treatment in some kinds of cancers. We aimed to evaluate the clinical efficacy of personalized targeted therapy for advanced biliary tract cancer (BTC) patients based on individual actionable mutations.
Methods
In this single-center study, the targeted next generation sequencing (NGS) was employed for consecutive 49 patients with BTC and the recommendation of biologic agent was offered according to most potentially targetable genetic alteration of each person. Among 32 patients with stage IV and R2 resection, 21 patients underwent conventional chemotherapy (mGEMOX), while the rest 11 patients received a personalized targeted agent alternative to chemotherapy. The progression-free survival (PFS), overall survival (OS) and disease control rate (DCR) were assessed.
Results
The genomic landscape of 49 patients demonstrated that TP53 (n = 31, 63.3%) variation was most prevalent and was followed by KRAS (n = 12, 24.5%), ARID1A (n = 6, 12.2%), PIK3CA (n = 6, 12.2%), SMAD4 (n = 6, 12.2%), CDKN2A (n = 5, 10.2%) and ERBB4 (n = 5, 10.2%). Further analysis of copy number alterations (CNAs) showed low recurrent amplified genes, such as PIK3CA, SMAD4, FGFR3, SRC, PIK3R2, CDK4, ERBB2, and CDK6. After a median follow-up of 12 months, the targeted group had a significant prolonged PFS (4.5 months vs. 1.5 months, P = 0.014) and a trend of prolonged OS (12.9 months vs. 4.1 months, P = 0.104) in comparison with the chemotherapy group. The DCR in targeted group was a little higher but without significance (63.6% vs. 33.3%, P = 0.142). In addition, the ratio of patients with more than Grade 2 treatment-related toxicities in the targeted therapy group was a little higher compared to that of chemotherapy group but without significance (36.4% vs. 19.0%, P = 0.397).
Conclusions
This mono-center small cohort study suggested that personalized targeted therapy for advanced BTC patients based on individual most potentially actionable mutation detected by NGS, which offered such patients a longer PFS and trends of better OS and DCR, could be an option alternative to conventional chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Funding
Science and Technology Commission of Shanghai Municipality (NO. 15411951900), National Natural Science Foundation of China (NO. 81472280), Special Fund on the Application and Transformation of Precision Medicine in Second Military Medical University (NO.2017JZ11).
Editorial Acknowledgement
There is not any editorial assistance for this abstract provided by a third party.
Disclosure
L. Xiong: Chairman, Chief Executive Officer: 3D Medicine, Inc. F. Li: Vice President: 3D Medicine, Inc. J.Y. Li, H. Qin, M. Han, D. Zhang: Employee: 3D Medicine, Inc. All other authors have declared no conflicts of interest.
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