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

• Published in: Oncotarget 2018-04, Vol.9 (28), p.19817-19825
• Main Authors: Kondo, Tomohiro, Kanai, Masashi, Kou, Tadayuki, Sakuma, Tomohiro, Mochizuki, Hiroaki, Kamada, Mayumi, Nakatsui, Masahiko, Uza, Norimitsu, Kodama, Yuzo, Masui, Toshihiko, Takaori, Kyoichi, Matsumoto, Shigemi, Miyake, Hidehiko, Okuno, Yasushi, Muto, Manabu
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.24865

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). 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, = 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. Complete coding exons of 12 HRR-related genes ( and ) 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. Our results suggest that inactivating HRR-related gene mutations are predictive of response to oxaliplatin-based chemotherapy in patients with PDAC.