Abstract CT217: POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors

mPaC patients (pts) with HRRm, including BRCA1 and/or BRCA2 mutations (BRCAm), derive benefit from platinum-based treatment (Pishvaian. J Clin Oncol 2019). In the Phase III POLO trial (NCT02184195) maintenance olaparib conferred a progression-free survival benefit over placebo in pts with a germline (g) BRCAm and mPaC. A prespecified exploratory analysis was conducted to determine the prevalence of tumor tissue biomarkers in pts screened for inclusion in POLO. Archival tumor samples were provided if available and, irrespective of subsequent pt randomization, DNA was analyzed using a gene panel from Foundation Medicine Inc. (FMI) or exome sequencing by Human Longevity Inc. (HLI). Results were compared with cohorts from FMI (mPaC; FoundationOne CDx panel) and The Cancer Genome Atlas (TCGA; primary and mPaC; exome sequencing). Tumor samples from 187/3315 (5.6%) pts screened for entry into POLO were available and sequenced. Prevalence of tumor HRRm in the POLO, FMI and TCGA cohorts are presented in the Table. The higher BRCAm prevalence observed in the POLO and FMI cohorts compared with TCGA may be due to sample size or differences in ethnicity or tumor sample location (primary vs metastatic). Mutations in BRCA2, BRCA1 and ATM were most common and were generally mutually exclusive. The prevalence of somatic (s) BRCAm in POLO was consistent with the FMI dataset (~2%); g and s BRCAm were mutually exclusive. Of the HRRm observed in non-BRCA genes, mutations in ATM were most prevalent. Prevalence of mutations in non-HRR genes (CDKN2A, SMAD4, KRAS, TP53) in POLO was consistent with that seen in other pancreatic cancer cohorts. In summary, based on the subgroup of pts with analyzed tumor tissue, the genetic profile of the screened POLO population is reflective of that seen in the overall pancreatic cancer population. ~8% of pts had tumors harboring a BRCAm, with mutations in BRCA2 more prevalent than BRCA1; ~7% of pts had tumors harboring a non-BRCA HRRm, most commonly in ATM (~5%). Citation Format: Zhongwu Lai, Talia Golan, Hedy L. Kindler, Brian Dougherty, Athena Matakidou, Liqin Dong, Gershon Locker, Elizabeth A. Harrington. POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT217.