Cell free circulating tumor DNA ERBB2 amplifications are targetable in patients with pancreatic ductal adenocarcinoma.

Abstract

282 Background: Molecularly targeted therapies have led to improved clinical benefit, however few targeted therapies exist in pancreatic ductal adenocarcinoma (PDAC). ERBB2 (HER2) amplifications (AMP) in PDAC have been described as potentially targetable, especially in KRAS wild type tumors. We describe the incidence of ERBB2 AMP in patients (pts) with PDAC who underwent cell-free circulating tumor DNA (cfDNA) testing with a CLIA/CAP/NYSDOH approved 73 gene assay. Methods: The Guardant Health Clinical Database was queried (March 2014-July 2017) for pts with a diagnosis of PDAC and an ERBB2 AMP identified on cfDNA (Guardant360). Copy number AMP ≥ 2.12 is reported. Pts with multiple cfDNA timepoints were included if an ERBB2 AMP was identified at any timepoint. Results: 30 pts met inclusion criteria (1.7% of pts with PDAC (1722)). Median age at test order was 63 years (range 24 to 92). 26 pts had one cfDNA timepoint, three pts had two, and one patient had three. In the pts with multiple timepoints, ERBB2 AMP was identified at one timepoint each for a total of 30 timepoints from 30 unique pts. In two pts, ERBB2 AMP was initially not detected (ND) and detected subsequently. In two pts, ERBB2 AMP was initially detected and subsequently ND. Median number of alterations per test was 6 (range 1 to 13). Median ERBB2 AMP was 2.47 copies (range 2.14 to 7.51). Concurrent KRAS single nucleotide variant was identified in 20 tests (66.7%); G12D(6), G12V(5), Q61H(1); G12D/ KRAS AMP(6), G12R/ KRAS AMP(2). Clinical follow-up was available for three pts, two of whom were treated with anti-HER2 therapy. One patient with a low ERBB2 AMP (2.20 copies) / KRAS wild type progressed on multiple lines of therapy. Following identification of cfDNA ERBB2 AMP, Traztuzumab was added to the FOLFOX regimen with clinical improvement and significant decline in CA19-9 (1,847 to 22 U/mL) over a four-month period. ERBB2 AMP decreased to undetected over the same period. For the past 8 months, patient has been on Trastuzumab alone with further decrease in CA19-9 (16 U/mL). Conclusions: cfDNA detects potentially targetable ERBB2 AMP in pts with PDAC, and targeted anti-HER2 therapy should be explored, even when these amplifications are detected at the lower range.