4.7 Article

Next-generation sequencing-guided molecular-targeted therapy and immunotherapy for biliary tract cancers

期刊

CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 70, 期 4, 页码 1001-1014

出版社

SPRINGER
DOI: 10.1007/s00262-020-02745-y

关键词

Biliary tract cancer; Next-generation sequencing; Immunotherapy; Targeted therapy; Personalized medicine

资金

  1. National Natural Science Foundation of China [81572434]
  2. Ministry of Science and Technology, National Science and Technology Major Special Project: Prevention and Treatment of Major Infectious Diseases such as AIDS and Viral Hepatitis [2018ZX10723204-007-001]
  3. Tianjin Health Commission [2017-1-35]
  4. Tianjin Medical University Cancer Institute [2018-2-8]
  5. (c) Young Medical Elites, Tianjin Health Commission [2017-1-35]
  6. Young Innovative Talents, Tianjin Medical University Cancer Institute and Hospital [2018-2-8]

向作者/读者索取更多资源

The study found that NGS-guided targeted therapy and immunotherapy may offer better prognosis for patients with advanced or relapsed biliary tract cancer compared to traditional chemotherapy. The type of gene mutation in patients can guide the selection of appropriate treatment drugs, and TMB is a useful biomarker for predicting the efficacy of immunotherapy.
Background Chemotherapy is a standard regimen for advanced or relapsed biliary tract cancer (BTC) with a 5-year overall survival (OS) rate of approximately 5% and a median OS of less than a year. Targeted therapies and immunotherapy aimed at providing more personalized treatments for BTCs have been tested. The objective of this study was to evaluate the effects of targeted therapy and immunotherapy on advanced BTC patients. Methods Twenty-four advanced/relapsed BTC patients were enrolled and examined with next-generation sequencing (NGS). Eight of them received NGS-guided targeted or immunotherapy, and the other 16 patients underwent routine chemotherapy. Comparison analysis of OS and objective response rate (ORR) was performed. Results IDH1, BRCA2, MAP2K1, and BRAF (V600E) were the major actionable genes mutated in this cohort. Patients who received NGS-guided therapy exhibited higher OS (not achieved vs. 6.5 months, p < 0.001) and ORR (87.5% vs. 25%, p < 0.001) than those without targetable mutations and who received first-line chemotherapy. BTCs harboring mutations in IDH1, ATM/BRCA2, or MAP2K1/BRAF (V600E) received treatment with dasatinib, olaparib, or trametinib, respectively. Three of the patients had high tumor mutation burden (TMB-H) and were treated with immune-checkpoint inhibitors and chemotherapy. All these patients achieved complete response or partial response. Conclusions NGS-guided targeted therapy and immunotherapy are promising personalized therapies for advanced or relapsed BTCs. TMB is a useful biomarker for predicting immunotherapy efficacy.

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