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Poster Discussion – Gastrointestinal tumours, non-colorectal

1484 - Genomic alterations predict clinical response to systemic chemotherapy and immune checkpoint blockade in biliary tract cancer

Date

28 Sep 2019

Session

Poster Discussion – Gastrointestinal tumours, non-colorectal

Presenters

Min Hwan Kim

Citation

Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247

Authors

M.H. Kim1, J. Yoon2, M. Jang3, H. Kim3, Y.N. Park3, M.G. Lee2, H.K. Hwang4, C.M. Kang4, W.J. Lee4, B. Kang1, H.C. Chung1, H.J. Choi1

Author affiliations

  • 1 Division Of Medical Oncology, Department Of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 2 Research Center For Human Genetics, Department Of Pharmacology, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 3 Department Of Pathology, Yonsei University College of Medicine, 03722 - Seoul/KR
  • 4 Division Of Hepatobiliary And Pancreatic Surgery, Department Of Surgery, Yonsei University College of Medicine, 03722 - Seoul/KR

Resources

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Abstract 1484

Background

Previous studies have identified several targetable oncogenic mutations in biliary tract cancer (BTC). However, reliable predictors of clinical response to therapeutic agents have not been established. This study aimed to identify predictors of clinical response to chemotherapy and immune checkpoint blockade in advanced BTC patients.

Methods

Genomic alterations in 54 patients with recurrent or metastatic BTC were investigated by targeted deep-sequencing for 524 key cancer genes using pre-treatment tumor tissues. The predictive value of genomic alterations, including mutational signatures, on response to chemotherapy and anti-PD-1/PD-L1 therapy, was assessed.

Results

Frequently altered genes included TP53 (50.0%), NOTCH1 (31.5%), KRAS (24.1%), KMT2C (22.2%), BAP1 (22.2%), and ERBB2 (22.2%). BAP1 deletion and NOTCH1 mutation were associated with a favorable response to chemotherapy. The homologous recombination deficiency (HRD)-associated signature (signature 3) was significantly higher in the responding patients to chemotherapy and a positive correlation between the HRD-signature and BAP1 deletion was observed, suggesting that HRD caused by BAP1 deletion may contribute to a favorable response to chemotherapy. A high proportion of signature 12 was associated with favorable overall and progression-free survival after chemotherapy. Among 19 patients treated with anti-PD-1/PDL1 therapy, the mismatch repair (MMR) deficiency–associated signatures (signatures 6, 15, 20, and 26) were significantly higher in the responding patients.

Conclusions

This study identified several predictors on therapeutic response of advanced BTC. BAP1 deletion and NOTCH1 mutation were predictors of a favorable response to chemotherapy. Furthermore, the mutational signatures associated with HRD and MMR significantly correlated with the response to chemotherapy and anti-PD-1/PD-L1 therapy, respectively.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National R&D Program for Cancer Control, Republic of Korea.

Disclosure

All authors have declared no conflicts of interest.

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