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Oncotarget. 2018 Apr 13;9(28):19817-19825. doi: 10.18632/oncotarget.24865. eCollection 2018 Apr 13.

Association between homologous recombination repair gene mutations and response to oxaliplatin in pancreatic cancer.

Author information

1
Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
2
Biomedical Department, Mitsui Knowledge Industry Co., Ltd., Tokyo, Japan.
3
Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
4
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
5
Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
6
Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan.

Abstract

Objectives:

We aimed to examine the association between homologous recombination repair (HRR)-related gene mutations and efficacy of oxaliplatin-based chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC).

Results:

Non-synonymous mutations in HRR-related genes were found in 13 patients and only one patient had a family history of pancreatic cancer. Eight patients with HRR-related gene mutations (group A) and nine without HRR-related gene mutations (group B) received oxaliplatin-based chemotherapy. Median progression-free survival after initiation of oxaliplatin-based chemotherapy was significantly longer in group A than in group B (20.8 months vs 1.7 months, p = 0.049). Interestingly, two patients with inactivating HRR-related gene mutations who received FOLFIRINOX as first-line treatment showed exceptional responses with respect to progression-free survival for > 24 months.

Materials and Methods:

Complete coding exons of 12 HRR-related genes (ATM, ATR, BAP1, BRCA1, BRCA2, BLM, CHEK1, CHEK2, FANCA, MRE11A, PALB2, and RAD51) were sequenced using a Clinical Laboratory Improvement Amendment-certified multiplex next-generation sequencing assay. Thirty consecutive PDAC patients who underwent this assay between April 2015 and July 2017 were included.

Conclusions:

Our results suggest that inactivating HRR-related gene mutations are predictive of response to oxaliplatin-based chemotherapy in patients with PDAC.

KEYWORDS:

BRCA; homologous recombination repair; oxaliplatin; pancreatic cancer; precision medicine

Conflict of interest statement

CONFLICTS OF INTEREST Masashi Kanai: Research funding from Taiho Pharmaceutical and stock ownership at Therabiopharma Inc. Tomohiro Sakuma and Hiroaki Mochizuki: employment, Mitsui Knowledge Industry. Muto Manabu: consulting or advisory role: QP, Eisai. Research funding: Olympus, Mitsui Knowledge Industry, Taiho Pharmaceutical, Chugai Pharma, Theravalues Corporation, Pfizer. All remaining authors have declared no conflicts of interest.

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