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

// Tomohiro Kondo 1 , Masashi Kanai 1 , Tadayuki Kou 1 , Tomohiro Sakuma 2 , Hiroaki Mochizuki 2 , Mayumi Kamada 3 , Masahiko Nakatsui 3 , Norimitsu Uza 4 , Yuzo Kodama 4 , Toshihiko Masui 5 , Kyoichi Takaori 5 , Shigemi Matsumoto 1 , Hidehiko Miyake 6 , Yasushi Okuno 3 and Manabu Muto 1 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 Correspondence to: Masashi Kanai, email: kanai@kuhp.kyoto-u.ac.jp 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.