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

Tomohiro Kondo; Masashi Kanai; Tadayuki Kou; Tomohiro Sakuma; Hiroaki Mochizuki; Mayumi Kamada; Masahiko Nakatsui; Norimitsu Uza; Yuzo Kodama; Toshihiko Masui; Kyoichi Takaori; Shigemi Matsumoto; Hidehiko Miyake; Yasushi Okuno; Manabu Muto

doi:10.18632/oncotarget.24865

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Research Papers:

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

Tomohiro Kondo _, Masashi Kanai, Tadayuki Kou, Tomohiro Sakuma, Hiroaki Mochizuki, Mayumi Kamada, Masahiko Nakatsui, Norimitsu Uza, Yuzo Kodama, Toshihiko Masui, Kyoichi Takaori, Shigemi Matsumoto, Hidehiko Miyake, Yasushi Okuno and Manabu Muto

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Abstract

Tomohiro Kondo1, Masashi Kanai1, Tadayuki Kou1, Tomohiro Sakuma2, Hiroaki Mochizuki2, Mayumi Kamada3, Masahiko Nakatsui3, Norimitsu Uza4, Yuzo Kodama4, Toshihiko Masui5, Kyoichi Takaori5, Shigemi Matsumoto1, Hidehiko Miyake6, Yasushi Okuno3 and Manabu Muto1

1Department of Medical Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

2Biomedical Department, Mitsui Knowledge Industry Co., Ltd., Tokyo, Japan

3Department of Biomedical Data Intelligence, Graduate School of Medicine, Kyoto University, Kyoto, Japan

4Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

5Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

6Clinical Genetics Unit, Kyoto University Hospital, Kyoto, Japan

Correspondence to:

Masashi Kanai, email: [email protected]

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

Received: August 24, 2017 Accepted: March 15, 2018 Published: April 13, 2018

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.

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Research Papers:

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

Abstract