Real-world timelines of BRCA1/2-related molecular testing in pancreatic cancer.

Abstract

601 Background: BRCA1/2 mutations are present in ̃6-8% of patients with pancreatic adenocarcinoma. Olaparib is a recently approved PARP inhibitor (PARPi) in the US and Europe for germline BRCA1/2-mutated metastatic PaC in the 1st line maintenance setting following response to at least 16 weeks of a platinum-containing regimen. However, the availability of BRCA1/2 testing results at the time of 1st line and subsequent treatment decisions in the advanced stage has not been established in real-world settings. Methods: Longitudinal clinical/molecular data collected between 1/2012-12/2020 were retrospectively analyzed in 75 PaC pts with germline or somatic BRCA1/2 mutations (BRCA1/2m) who enrolled in Perthera’s US real-world observational registry. Tumor NGS testing results were generated by commercial labs for all patients. Germline status was assessed by a molecular tumor board when testing results are available. BRCA1/2m discovery timing (days since advanced presentation), molecular testing turnaround time (days from physician order to result), and platinum utilization were abstracted from physician records. Associations between BRCA1/2m discovery timing and platinum utilization were evaluated using Fisher’s exact test. Results: At the time of advanced PaC diagnosis, BRCA1/2m status was known in a minority of patients (29% (22 of 75). In the remaining 71% (53 of 75) patients, the median time to report BRCA1/2m status was 76 days (IQR=56-558) following advanced diagnosis. The median tumor NGS testing turnaround time was 35 days after physician order (IQR=24-54). Platinum use in any setting was documented in 85% (64 of 75) of patients and the majority of these patients (62%, 40 of 64) initiated a platinum-based regimen before BRCA1/2m status was first reported. Platinum agents were initiated before 2nd line in 75% (48 of 64) patients, and this was associated with BRCA1/2m identification before advanced diagnosis (p=0.03). Conclusions: BRCA1/2 testing results may not always be available when 1st line regimens are chosen which can impact ideal treatment sequencing in PaC patients. These real-world analyses underscore the importance of upfront BRCA1/2 testing in PaC patients.