T. Katada1, H. Ichikawa1, Y. Hirose1, M. Nagahashi1, Y. Shimada1, T. Hanyu1, T. Ishikawa1, Y. Kano1, Y. Muneoka1, J. Sakata1, T. Kobayashi1, H. Kameyama1, T. Wakai1 1Niigata University Graduate School of Medical and Dental Sciences,Division Of Digestive And General Surgery,Niigata, NIIGATA, Japan
Introduction: Defective homologous recombination (HR) due to genetic alteration of HR genes contributes to a high response of platinum therapy in ovarian and breast cancers. The aim of this study is to clarify the clinical significance of defective HR in platinum-based chemotherapy for gastric cancer (GC).
Methods: A total of 26 patients (19 men and 7 women, with a median age of 66 years) who underwent platinum-based chemotherapy for unresectable metastatic GC were enrolled. Metastatic sites after gastrectomy were lymph node in 10 (38%), liver in 8 (31%), peritoneum in 8 (31%), others in 2 (8%) patients. Genetic alterations of HR genes (BRCA1, BRCA2, RAD50, RAD51C, RAD51D, BLM, PALB2 and FANCD2) in the primary tumor were assessed by cancer gene-panel. We evaluated the association between defective HR and treatment response (RECIST ver. 1.1), progression free survival (PFS) and overall survival (OS).
Results: BRCA1, BRCA2, RAD50, BLM, and FANCD2 mutations were shown in 3 (12%), 2 (8%), 2 (8%), 1 (4%) and 1 patient (4%), respectively. Overall, 6 patients (23%) had genetic alterations of HR genes (defective HR group). Objective response rate (complete or partial response) was 60% in the defective HR group and 27% in the proficient HR group (P = 0.29). Disease control rate (complete or partial response or stable disease) was 100% in the defective HR group and 47% in the proficient HR group (P = 0.06). PFS was significantly longer in the defective HR group than in the proficient HR group (median 6 months vs. 3 months; P = 0.035). OS was also significantly longer in the defective HR group than in the proficient HR group (median 18 months vs. 8 months; P = 0.025).
Conclusions: Genetic alteration of HR genes was significantly associated with a high response of platinum-based chemotherapy and favorable patient outcome in unresectable metastatic GC. Clinical utility of the assessment of defective HR in GC is worth considering further large-scale validation studies.