Abstract 133P
Background
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).
Methods
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.
Results
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: 133P
HER2 status per cancer type
| Cancer Type (N>10) | Total | CNV + mRNA + IHC + | CNV+ mRNA + IHC - | CNV+ mRNA- IHC+ | CNV- mRNA+ IHC+ | CNV+ mRNA- IHC- | CNV- mRNA+ IHC- | CNV- mRNA- IHC+ | Any + | |||||||
| N | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % |
| Multi-institution | Breast | 260 | 35 | 13.5 | – | – | 12 | 4.6 | – | 44 | 16.9 | 8 | 3.1 | 99 | 38.1 | |
| Colon | 88 | 4 | 4.5 | – | – | 2 | 2.3 | – | 32 | 36.4 | 2 | 2.3 | 40 | 45.5 | ||
| NSCLC | 64 | 1 | 1.6 | – | – | 16 | 25 | – | 30 | 46.9 | 2 | 3.1 | 49 | 76.6 | ||
| Pancreas | 34 | – | – | – | 3 | 8.8 | – | 16 | 47.1 | 1 | 2.9 | 20 | 58.8 | |||
| Ovary | 30 | 1 | 3.3 | – | – | 2 | 6.7 | – | 6 | 20 | 1 | 3.3 | 10 | 33.3 | ||
| Sarcoma | 27 | – | ||||||||||||||
| CUP | 25 | 2 | 8 | – | – | 1 | 4 | 1 | 4 | 1 | 4 | 4 | 16 | 9 | 36 | |
| Prostate | 21 | – | – | – | – | – | 1 | 4.8 | 1 | 4.8 | 2 | 9.5 | ||||
| Hepatobiliary | 20 | 2 | 10 | – | – | – | – | 1 | 5 | 1 | 5 | 4 | 20 | |||
| Bladder | 19 | 4 | 21.1 | – | – | 4 | 21.1 | – | 1 | 5.3 | 1 | 5.3 | 10 | 52.6 | ||
| Gastroesophageal | 16 | 2 | 12.5 | – | 1 | 6.3 | – | – | 1 | 6.3 | 1 | 6.3 | 5 | 31.3 | ||
| H&N | 14 | – | ||||||||||||||
| Rectal | 14 | 2 | 14.3 | 1 | 7.1 | – | – | – | 5 | 35.7 | – | 8 | 57.1 | |||
| Appendix | 11 | – | ||||||||||||||
| UCSD | 53 | 2 | 3.8 | – | – | 4 | 7.5 | – | 13 | 24.5 | 3 | 5.7 | 22 | 41.5 |
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Paradigm Diagnostics.
Disclosure
R. Kurzrock: Shareholder/Stockholder/Stock options, Stock and other equity interests: IDbyDNA; Shareholder/Stockholder/Stock options, Stock and other equity interests: CureMatch, Inc.; Shareholder/Stockholder/Stock options, Stock and other equity interests: Soluventis; Advisory/Consultancy, Consulting or Advisory Role: Gaido; Advisory/Consultancy, Consulting or Advisory Role: LOXO; Advisory/Consultancy, Consulting or Advisory Role: X-Biotech; Advisory/Consultancy, Consulting or Advisory Role: Actuate Therapeutics,; Advisory/Consultancy, Speaker Bureau/Expert testimony, Consulting or Advisory Role and speaker: Roche; Advisory/Consultancy, Consulting or Advisory Role: NeoMed; Advisory/Consultancy, Consulting or Advisory Role: Soluventis; Advisory/Consultancy, Research grant/Funding (institution), Consulting or Advisory Role: Pfizer; Advisory/Consultancy, Consulting or Advisory Role: Merck; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Sequenom; Research grant/Funding (institution): Foundation Medicine; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Grifols; Research grant/Funding (institution): Konica Minolta; Research grant/Funding (institution): DeBiopharm; Research grant/Funding (institution): Boerhringer Ingelheim; Research grant/Funding (institution): OmniSeq; Officer/Board of Directors: CureMatch, Inc.; Officer/Board of Directors: CureMetrix, Inc. S. Kato: Advisory/Consultancy, Consultant: Foundation medicine ; Speaker Bureau/Expert testimony, Speaker: Roche. All other authors have declared no conflicts of interest.