Association between homologous recombination gene variants and efficacy of oxaliplatin-based chemotherapy in advanced pancreatic cancer: prospective multicenter observational study

Abstract

Next-generation sequencing (NGS)-based gene profiling can identify patients with pancreatic cancer with homologous recombinant repair gene pathogenic variants (HRRv). Several retrospective studies have reported a positive association between HRRv and the efficacy of platinum-based chemotherapy. However, this association remains to be validated in a prospective study. This multicenter, prospective, observational study included patients with histologically confirmed unresectable or recurrent pancreatic cancer who required systemic chemotherapy. Patients who were oxaliplatin-naïve patients were eligible. The HRRv status was measured using a College of American Pathologists-accredited NGS panel. One-year overall survival rate (1yr-OS%) was calculated after initiation of oxaliplatin-based chemotherapy and was set as the primary endpoint. Forty patients were enrolled between August 2018 and March 2020. The NGS success rate was 95% (38/40). HRRv was detected in 11 patients (27.5%). Oxaliplatin-based chemotherapy was administered to 9 of 11 patients with HRRv (81.8%) and 15 of 29 patients with non-HRRv (51.7%). The 1yr-OS% after initiation of oxaliplatin-based chemotherapy was 44.4% [95% confidence interval (CI) 13.7-71.9] and 57.1% (95% CI 28.4-78.0) in HRRv-positive and -negative cohorts, respectively. These data suggested that HRRv status alone could not be a potential predictive marker of oxaliplatin-based chemotherapy in patients with advanced pancreatic cancer. These results were in line with the results of a recent phase II study reporting the limited efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitor in patients with pancreatic cancer who harbored HRRv other than BRCA. Future studies investigating patients with biallelic HRRv in the first-line setting are warranted.Trial registration UMIN000033655.

Keywords: BRCA; Homologous recombination repair; Oxaliplatin; Pancreatic cancer; Precision medicine.