Somatic Genomic Testing for Metastatic or Advanced Cancer

Publication Date: February 16, 2022
Last Updated: March 27, 2023

Diagnosis

Provisional Clinical Opinions (PCOs)

Section 1: Multigene Panel-Based Genomic Sequencing with Disease-Specific Approved Markers

PCO 1.1
Genomic testing should be performed for patients with metastatic or advanced solid tumors with adequate performance status in the following two clinical scenarios:
  • When there are genomic biomarker-linked therapies approved by regulatory agencies for their cancer.
  • When considering a treatment for which there are specific genomic biomarker-based contraindications or exclusions.
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PCO 1.2.1
For patients with metastatic or advanced solid tumors, genomic testing using multigene genomic sequencing is preferred whenever patients are eligible for a genomic biomarker-linked therapy that a regulatory agency has approved. (, , M )
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PCO 1.2.2
Multigene panel-based genomic testing should be used whenever more than one genomic biomarker is linked to a regulatory agency-approved therapy. (, , S )
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PCO 1.3
If the genomic sequencing results are used to inform clinical care, such testing must be performed in an appropriately certified laboratory. (, , S )
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PCO 1.4
Clinical decision-making should incorporate:
  1. The known or predicted impact of a specific genomic alteration on protein expression or function and
  2. clinical data on the efficacy of targeting that genomic alteration with a particular agent.
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PCO 1.5
Germline testing for genetic alterations linked to approved therapies should be performed in patients with metastatic or advanced solid tumors considered for such treatment. It should not be limited by family history-based or clinical criteria used for familial risk assessment. Patients with P/LP variants should be referred for genetic counseling for education about secondary cancer risks, possible inheritance of germline mutations among blood relatives, and the differences between germline and somatic mutations, if they did not receive pretest counseling. (, , S )
Qualifying statement: Germline testing and genetic counseling may still be needed in patients with personal or family histories suggestive of an inherited predisposition, even when no germline alterations are identified during tumor genomic sequencing using various sequencing panels.
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Section 2: Assessment of dMMR and/or MSI-H Status, and TMB

PCO 2.1
dMMR status should be evaluated on patients with metastatic or advanced solid tumors who are candidates for immunotherapy.
  • There are multiple approaches, including using large multigene panel-based testing to assess MSI.
  • Consider the prevalence of dMMR and/or MSI-H status in individual tumor types when making this decision
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PCO 2.2
When TMB may influence the decision to use immunotherapy, testing should be performed with either large multigene panels with validated TMB testing or whole-exome analysis. (, , S )
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Section 3: Testing for Gene Fusions and Exon Skipping Variants

PCO 3.1
In patients with metastatic or advanced solid tumors, fusion testing should be performed if there are fusion-targeted therapies with regulatory approval for that specific disease. (, , S )
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PCO 3.2.1
Neurotrophic tyrosine receptor kinase (NTRK) fusion testing should be performed in patients with metastatic or advanced solid tumors who may be candidates for tyrosine receptor kinase (TRK)-inhibitor therapy, considering the prevalence of NTRK fusions in individual tumor types. (, , M )
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PCO 3.2.2
Testing for other fusions is recommended in patients with metastatic or advanced solid tumors if no oncogenic driver alterations are identified on large panel DNA sequencing (, , M )
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PCO 3.3
Testing for MET exon 14 skipping should be performed for patients with all types of non-small cell lung cancer (NSCLC). (, , S )
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Section 4: Diseases with No Approved Disease-Specific Markers

PCO 4.1
Genomic testing should be considered to determine candidacy for tumor-agnostic therapies in patients with metastatic or advanced solid tumors without approved genomic biomarker-linked therapies. (, , M )
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PCO 4.2
For tumors with actionable genomic alterations without approved genomic biomarker-linked targeted therapies, patient participation in clinical trials is encouraged after considering the expected efficacy of available standard-of-care options. (, , S )
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PCO 4.3
Off-label and off-study use of genomic biomarker-linked therapies approved in other diseases is NOT recommended when a clinical trial is available or without clinical evidence of meaningful efficacy. (, , S )
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Section 5: Elements to Consider While Reviewing Genomic Testing Results

Tumor only testing versus matched tumor-normal testing:
Tests should clearly state whether only the tumor was sequenced or whether both the tumor and a patient-matched normal sample was sequenced. The reporting strategy for P/LP germline alterations should be clearly stated. (, , )
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Targeted sequencing approach: Multigene panel-based sequencing reports should specify which of the two methods is used:
  • Amplicon sequencing or
  • multiplex polymerase chain reaction (PCR) amplification of select gene DNA or genomic mutational hotspots using sequence specific primers.
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Genes tested: Multigene panel-based sequencing reports should clearly state which genes were included; if the whole gene was sequenced or only its hotspots, or testing of select exons, or introns. Sequencing reports should also include which, if any, regions failed analysis and reason for sequencing failure. (, , )
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Description of genomic alterations should include:
  • The nucleotide change, position of the change within DNA, variant type, variant consequence on the gene products, and, when applicable, amino acid change using Human Genome Variation Society (HGVS) nomenclature.
  • The functional significance of the alteration.
  • Whether fusions are tested, and if so, which ones.
  • The known or unknown therapeutic implications of the alteration within the patient’s tumor type with clinically available therapies.
  • Mutational clonality: Inclusion of VAF and copy number which may help with treatment selection.
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ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the opportunity to participate.
Additional information, which may include data supplements, slide sets, and other clinical tools and resources, is available at www.asco.org/assays-and-predictive-markers-guidelines.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Somatic Genomic Testing in Patients with Metastatic or Advanced Cancer

Authoring Organization

American Society of Clinical Oncology

Publication Month/Year

February 16, 2022

Last Updated Month/Year

October 1, 2024

Document Type

Guideline

Country of Publication

US

Document Objectives

An ASCO provisional clinical opinion offers timely clinical direction to ASCO's membership following publication or presentation of potentially practice-changing data from major studies. This provisional clinical opinion addresses the appropriate use of tumor genomic testing in patients with metastatic or advanced solid tumors.

Target Patient Population

Patients with metastatic or advanced solid tumors

Target Provider Population

Oncologists, pathologists, and other clinicians involved in deciding appropriate care for patients with metastatic or advanced cancer

PICO Questions

  1. For what clinical scenarios are there biomarker-linked regulatory approvals for the treatment of specific genomic alterations?

  2. When should multigene panel–based genomic testing be performed when there is only a single genomic biomarker or small numbers of genomic biomarkers linked to regulatory approvals of anticancer drugs?

  3. What are other important considerations when ordering and interpreting genomic testing?

  4. What is the role of multigene panel–based tumor genomic sequencing in dMMR and/or microsatellite instability-high testing?

  5. What is the role of multigene panel–based tumor genomic sequencing in TMB testing?

  6. When should patients be tested for fusions?

  7. When should patients be tested for fusions outside of disease-specific approvals?

  8. What evidence of actionability should be present for a clinician to recommend a therapy on the basis of panel testing in the absence of approved indications?

Inclusion Criteria

Male, Female, Adolescent, Adult, Child, Older adult

Health Care Settings

Hospital, Laboratory services, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Assessment and screening

Diseases/Conditions (MeSH)

D014408 - Biomarkers, Tumor, D000088744 - Genomic Medicine

Keywords

Somatic Tumor Testing, genomic

Source Citation

Chakravarty D, Johnson A, Sklar J, et al. Somatic Genomic Testing in Patients with Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion. J Clin Oncol. 2022 Feb 17. doi:10.1200/JCO.21.02767

Supplemental Methodology Resources

Data Supplement, Evidence Tables