133P HER2 transcription status of diverse solid tumours with clinical implications

Abstract

Utility of HER2 mRNA expression as a potential therapeutic biomarker is unclear. We previously reported the discordant HER2 status between copy number variation (CNV), mRNA and immunohistochemistry (IHC) from a large multi-institute dataset. Herein, we investigated comprehensive HER2 status by cancer (CA) type with clinical outcome among HER2 positive patients (pts) at University of California San Diego (UCSD). By Paradigm Diagnostics (CLIA-certified laboratory), HER2 status was evaluated using IHC, qRT-PCR and NGS between 2015-2019. We evaluated pts who had all three HER2 testing available by tumor type, with UCSD outcomes included. Of 5,305 pts, 723 had CNV, mRNA and IHC evaluated (Table). Among diverse solid tumors, HER2 positivity in at least one test were seen in 76.6% (49/64) of NSCLC and 58.8% (20/34) of pancreas CA. Sole mRNA positivity (CNV-/IHC-) were found ≥35% in NSCLC, pancreatic and colorectal cancers. Among 53 UCSD pts who had all three HER2 testing, 22 pts had ≥ 1 positive HER2 test (including 24.5% [13/53] pts with mRNA+ only). We identified 7 pts that were given Anti-HER2 therapy (Tx). One pt with CNV+/mRNA+/IHC+ metastatic esophageal CA achieved complete response with chemotherapy plus trastuzumab followed by trastuzumab maintenance (progression-free survival [PFS]: 48 + months). One pt with metastatic cholangiocarcinoma mRNA+ (CNV and IHC unable to perform) achieved durable partial response with dual-anti-Her2 Tx (trastuzumab and lapatinib) (PFS: 24+ months). In contrast, 5 pts had poor outcomes despite anti-HER2 Tx, given after 3-5 previous Tx lines.Table 133PHER2 status per cancer typeCancer Type (N>10)TotalCNV + mRNA + IHC +CNV+ mRNA + IHC -CNV+ mRNA- IHC+CNV- mRNA+ IHC+CNV+ mRNA- IHC-CNV- mRNA+ IHC-CNV- mRNA- IHC+Any +NN%N%N%N%N%N%N%N%Multi-institutionBreast2603513.5––124.6–4416.983.19938.1Colon8844.5––22.3–3236.422.34045.5NSCLC6411.6––1625–3046.923.14976.6Pancreas34–––38.8–1647.112.92058.8Ovary3013.3––26.7–62013.31033.3Sarcoma27–CUP2528––141414416936Prostate21–––––14.814.829.5Hepatobiliary20210––––1515420Bladder19421.1––421.1–15.315.31052.6Gastroesophageal16212.5–16.3––16.316.3531.3H&N14–Rectal14214.317.1–––535.7–857.1Appendix11–UCSD5323.8––47.5–1324.535.72241.5 Open table in a new tab We found diverse HER2 expression patterns among solid tumors, including difficult to treat cancer of unknown primary, pancreatic CA, and hepatobiliary CA. Although it is a small cohort, patients with HER2 mRNA overexpression could respond to anti-HER2 regimen. Further clinical investigation is warranted.