Companion Diagnostic, Targeted Therapy Approvals Rise in Tandem

As precision medicine evolves in oncology, companion diagnostics are broadly and increasingly being adopted to guide treatment decisions, enabling clinicians to better and more precisely direct patients to therapies that best suit their unique genomic profiles.

Shridar Ganesan, MD, PhD

In 2020, the rate of companion diagnostic approvals is keeping pace with that of targeted therapies, rapidly expanding the arsenal of novel tools available to identify actionable molecular markers across histologies.

Since January 2020, the FDA has approved 10 new single-agent and combination regimens for use with a specific companion diagnostic (Table).1,2

The agency also has given the go-ahead for the Ventana HER2 Dual ISH DNA Probe Cocktail assay, a new, faster method for detecting HER2 gene amplification status for trastuzumab (Herceptin) therapy.2

Additionally, on August 7, 2020, the agency approved Guardant360 CDx assay, a next-generation sequencing (NGS) test that utilizes circulating cell-free DNA from peripheral whole blood plasma, as a companion diagnostic to detect EGFR mutations in patients with non-small cell lung cancer who are candidates for osimertinib (Tagrisso) therapy. The test is the first liquid biopsy assay that also uses NGS technology, the FDA said.3

As precision medicine evolves in oncology, companion diagnostics are broadly and increasingly being adopted to guide treatment decisions, enabling clinicians to better and more precisely direct patients to therapies that best suit their unique genomic profiles. Specifically, companion diagnostics can be used to select the patients who are likely to respond to a given therapeutic intervention, as well as those who should not receive a specific treatment because of a high risk of adverse events. This latter insight is critical, considering that many oncology drugs are toxic and have a positive effect in only a fraction of patients with a particular malignancy.4

The profusion of targeted therapies approved with associated companion diagnostics in 2020 duly reflects oncology’s growing emphasis on personalized methodologies of treatment selection and the field’s continuous investigative efforts to advance precision medicine, according to Shridar Ganesan, MD, PhD, associate director for Translational Science and section chief of Molecular Oncology at the Rutgers Cancer Institute of New Jersey in New Brunswick. “What we are seeing is the result of a lot of investment in targeted therapeutics and approaches over the past decade now coming to fruition,” Ganesan said.


The FDA has approved 43 in vitro and imaging-based diagnostic devices, including the Guardant360 CDx assay.2,3

This record of FDA-accepted companion diagnostics dates back to 1998, when Dako Denmark’s immunohistochemical assay, HercepTest, developed to detect the HER2 protein in breast cancer tissue, was concurrently approved with trastuzumab (Herceptin).

The simultaneous approval represented the first step toward oncology’s current practice of codeveloping drugs and corresponding diagnostics.5

In contrast to 1998, this model of companion diagnostic-guided therapeutics is now dominant in oncology, with several devices holding indications for multiple therapies across tumor types. For example, Foundation Medicine’s NGS–based in vitro diagnostic device, FoundationOne CDx, which detects substitutions, insertion and deletion alterations, and copy number alterations in 324 genes, is approved as a companion diagnostic test for 23 therapies. The assay uses DNA isolated from formalin-fixed, paraffin-embedded tumor tissue specimens.

On April 17, 2020, Foundation Medicine announced that the comprehensive genomic profiling test received FDA clearance to aid the identification of candidates for pemigatinib (Pemazyre) monotherapy, which received an accelerated approval for adults with treatment-naïve, unresectable, locally advanced, or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement.6

FoundationOne CDx’s indication further expanded on May 6, 2020, when the FDA granted capmatinib (Tabrecta) an accelerated approval for adults with metastatic MET exon14 skipping—mutated non–small cell lung cancer and designated the device as the agent’s corresponding companion diagnostic.7

The approval of FoundationOne CDx for multiple tumor types exemplifies Ganesan’s observation that companion diagnostic development does not always entail new technology and will not necessarily require frequent innovation as the usage and utility of these devices expands in oncology. “Often, we are building on a platform diagnostic that is already FDA approved. In some cases, new diagnostic tools are not being invented; rather, existing assays are being validated for a new purpose,” Ganesan said.

On May 19, 2020, FoundationOne CDx was approved to support the identification of patients with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer. Patients with the biomarker who progress after prior treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga) are eligible to receive olaparib (Lynparza).8

This decision expanded FoundationOne CDx’s olaparib-specific indication: the diagnostic was previously approved to select patients with BRCA-mutant advanced ovarian cancer who would benefit from frontline maintenance olaparib monotherapy, on July 1, 2019.9

FoundationOne CDx’s 2019 approval followed a 2016 announcement issued by AstraZeneca, olaparib’s developer, and Foundation Medicine indicating that the companies had entered into a definitive agreement to develop a novel companion diagnostic assay for olaparib to support the global development of the PARP inhibitor.10

The cross-therapy companion diagnostic approvals that FoundationOne CDx received in the 4 years that followed AstraZeneca and FoundationOne’s forging of this strategic partnership evidence the multiyear nature of the research efforts required to advance diagnostic-guided precision care. Ganesan emphasized that moving the needle in personalized medicine can be a slow process fraught with questions, even if the recent succession of 2020 companion diagnostic approvals makes it appear otherwise.

“For example, it took us over 20 years to go from identifying HER2 amplification in a subset of breast cancer, to developing and validating HER2–targeted theraputics, and f inally, development of combination treatment strategies that have changed the natural history of early and late-stage HER2amplified breast cancers,” Ganesan said.

Nevertheless, the series of 2020 companion diagnostic indications that the FDA has issued in synchronization with targeted therapy approvals represents “a very important series of developments that points to the importance of upfront molecular profiling for many cancers, both as part of their biologic classification and to guide optimal therapy,” Ganesan added.


1. Hematology/oncology (cancer) approvals & safety notifications. FDA. Updated August 6, 2020. Accessed August 10, 2020.

2. List of cleared or approved companion diagnostic devices (in vitro and imaging tools). FDA. Updated August 3, 2020. Accessed August 10, 2020.

3. FDA approves first liquid biopsy next-generation sequencing companion diagnostic test. FDA. August 7, 2020. Accessed August 10, 2020.

4. Becker Jr R, Mansfield E. Companion diagnostics. Clin Adv Hematol Oncol. 2010;8(7):478-479.

5. Jan Trøst Jørgensen, ed. Companion and Complementary Diagnostics: From Biomarker Discovery to Clinical Implementation. Academic Press; 2019.

6. Foundation Medicine receives FDA approval for FoundationOne CDx as the companion diagnostic for Pemazyre (pemigatinib), the first FDA-approved targeted therapy for adults with previously treated locally advanced or metastatic cholangiocarcinoma. News release. Foundation Medicine, Inc; April 17, 2020. Accessed July 13, 2020.

7. Foundation Medicine receives FDA approval for FoundationOne CDx as the companion diagnostic for Tabrecta (capmatinib), the only FDA-approved MET inhibitor for patients with metastatic non–small cell lung cancer with METex14. News release. Foundation Medicine, Inc; May 6, 2020. Accessed July 13, 2020.

8. Foundation Medicine receives FDA approval for FoundationOne CDx as the companion diagnostic for Lynparza to identify patients with HRR-mutated metastatic castrationresistant prostate cancer. News release. Foundation Medicine, Inc; May 20, 2020. Accessed July 13, 2020.

9. Foundation Medicine expands indication for FoundationOne CDx as a companion diagnostic for Lynparza (Olaparib). News release. Foundation Medicine, Inc; July 1, 2019. Accessed July 13, 2020.

10. AstraZeneca and Foundation Medicine enter strategic collaboration for Lynparza companion diagnostic assay. News release. AstraZeneca; June 4, 2016. Accessed July 13, 2020.

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