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Review
. 2021 Jul 23:11:676939.
doi: 10.3389/fonc.2021.676939. eCollection 2021.

A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer

Jan Trøst Jørgensen  1 , Henrik Winther  2 , Jon Askaa  3 , Lena Andresen  4 , Dana Olsen  4 , Jens Mollerup  4
Affiliations
Review

A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer

Jan Trøst Jørgensen et al. Front Oncol. .

Abstract

The development of trastuzumab (Herceptin®) was one of the most significant cancer drug development projects of the 20th century. Not only was it a scientific and medical achievement but it also paved the way for the drug-diagnostic codevelopment model, where a predictive biomarker assay is developed in parallel to the drug. One of the challenges in the development of trastuzumab was to select the right patient population likely to respond and here, it was critical to have access to an accurate, robust and reliable assay for detection of HER2 overexpression in tumors. In the clinical development of trastuzumab, a clinical trial assay (CTA), developed by Genentech, was used for selection of HER2 positive patients. However, during the phase III trial with trastuzumab, a new optimized IHC assay, HercepTest™ was designed and developed by Dako. In the final stage of its development, a comparative study with the CTA was conducted in order to show concordance between the two assays. In September 1998, the Food and Drug Administration (FDA) simultaneously granted approval to trastuzumab and HercepTest™. The assay has been used for patient selection in a number of significant breast cancer clinical trials such as the HERA, CLEOPATRA, EMILIA and more. In these trials, HercepTest™ demonstrated its clinical utility in the neoadjuvant, adjuvant, and metastatic setting as well as in relation to different types of HER2 targeted therapies. Likewise, the assay was used for selection of HER2 positive gastric cancer patients in the important ToGA trail. HercepTest™ was the first companion diagnostic ever approved by the FDA, and more than 20 years of use has documented its clinical impact.

Keywords: HercepTest; ado-trastuzumab emtansine; breast cancer; companion diagnostics; drug-diagnostic codevelopment; gastric cancer; pertuzumab; trastuzumab.

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Conflict of interest statement

The authors have all been involved in the development of either first and/or second generation HercepTest™. JTJ is a former employee of Dako and has worked as a consultant for Agilent Technologies, Euro Diagnostica, Oncology Venture, Azanta, Alligator Biosciences, and Leo Pharma and has given lectures at meetings sponsored by AstraZeneca, Merck Sharp & Dohme, and Roche. JTJ is employed by Dx-Rx Institute. HW is a former employee of Dako and currently an employee of Biovica International AB. JA is a former employee of Dako and Genentech and has worked as a consult for Medical Prognosis Institute, Oncology Venture, and Inbiomotion SL. LA, DO, and JM are employees of Agilent Technologies Denmark ApS, previously Dako, and are shareholders of Agilent Technologies Inc. The authors declare that this article received funding from Dx-Rx Institute. The funder had the following involvement with the article: JTJ is an employee of the Dx-Rx Institute that paid the publication fee.

Figures

Figure 1
Figure 1
Milestones for the development of HercepTest™ and different HER2 targeted therapies. CTA, Clinical Trial Assay; FDA, Food and Drug Administration; BC, Breast Cancer; GEA, Gastroesophageal junction adenocarcinoma; Herceptin®, trastuzumab; Perjeta®, pertuzumab; Kadcyla®, ado-trastuzumab emtansine/TDM1.
Figure 2
Figure 2
Breast carcinoma stained with HercepTest™, IHC3+ score.
Figure 3
Figure 3
Adenocarcinoma of the stomach stained with HercepTest™, IHC3+ score.
See this image and copyright information in PMC

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