Somatic Genomic Testing for Metastatic or Advanced Cancer

Publication Date: February 17, 2022

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.
(, , S )
614
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 )
614
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 )
614
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 )
614
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.
(, , S )
614
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.
614

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
(, , S )
614
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 )
614

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 )
614
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 )
614
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 )
614
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 )
614

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 )
614
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 )
614
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 )
614

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. (, , )
614
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.
(, , )
614
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. (, , )
614
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.
(, , )
614
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

Publication Month/Year

February 17, 2022

Document Type

Guideline

Country of Publication

US

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