AMP/CAP Guidelines for Lung Cancer MDX: Open Comment on New Guidelines

Guidelines are increasingly impactful on payers, from the non invasive prenatal testing field (NIPT) to cancer in the elderly.  A new edition of the Lung Biomarkers guideline is up for public comment.   This guideline was last released in 2013 (as Lindeman et al.), and is a joint work product of the College of American Pathologists, the Association for Molecular Pathology, and the International Association for the Study of Lung Cancer (CAP, AMP, IASLC).

Access the relevant draft documents and enter your comment via the AMP website, here.
Comments are open til August 2, 2016.

Key questions clipped and pasted below the break.

Molecular Testing Guideline for 

Selection of Lung Cancer Patients – Revision

Key Questions

As seen on:

http://amp.org/committees/clinical_practice/AMPclinicalpracticeguidelines/documents/2-20160613CAPIASLCAMPLungMeetingscopeandkeyquestions_FINAL.pdf

Research questions I-IV relate to patients diagnosed with non-squamous, non-small cell lung cancer of all stages:

I.      What other genes, previously not addressed, should be tested in lung adenocarcinoma?

1.      In patients who are being considered for therapy with EGFR tyrosine kinase inhibitors or

MEK inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for KRAS molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for mutation within the KRAS gene, compared to when individuals are not tested for KRAS mutation?

c.   When screening for mutations within the KRAS gene, what are the clinical performance characteristics of the available assays?

2.   In patients who are being considered for therapy with ROS1 tyrosine kinase inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for ROS1 molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for any rearrangement/translocation within the ROS1 gene, compared to when individuals are not tested for ROS1 mutation?

c.   When screening for rearrangement/translocation within the ROS1 gene, what are the clinical performance characteristics of the available assays, including, FISH, IHC and advanced sequencing?

3.   In patients who are being considered for therapy with RET tyrosine kinase inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for RET molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for fusion and rearrangement/translocation within the RET gene, compared to when individuals are not tested for RET mutation?

c.   When screening for fusion and rearrangement/translocation within the RET gene, what are the clinical performance characteristics of the available assays, including FISH, IHC, RT-PCR, digital PCR, and advanced sequencing?

4.   In patients who are being considered for therapy with MET tyrosine kinase inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for MET molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for expression, overexpression, amplification, or mutations of the MET gene, compared to when expression levels are not tested within individuals?

c.   When screening for expression, overexpression, amplification, or mutations of the MET gene, what are the clinical performance characteristics of the available assays, including FISH, IHC and advanced sequencing?

5.   In patients who are being considered for therapy with BRAF inhibitors or EGFR tyrosine kinase inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for BRAF molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for mutation within the BRAF gene, compared to when individuals are not tested for BRAF mutation?

c.   Are there differences in clinical outcomes for patients with different alterations of the BRAF gene?

d.   When screening for mutation within the BRAF gene, does IHC provide equivalent performance characteristics to molecular based methods?

6.   In patients who are being considered for therapy with HER2/ERBB2 tyrosine kinase inhibitors;

a.   What demographic, histopathologic and clinical characteristics should be used to select patients for HER2/ERBB2 molecular testing?

b.   Are there downstream improvements in clinical outcomes when individuals are tested for mutation and amplification/overexpression of the HER2/ERBB2 gene, compared to when HER2/ERBB2 mutations are not tested within individuals?

c.   When screening for mutations and amplification/overexpression of the HER2/ERBB2 gene, what are the clinical performance characteristics of the available assays, including FISH, IHC and advanced sequencing?

7.   When conducting molecular testing of KRAS, ROS1, RET, MET, BRAF and HER2/ERBB2, what technical validation experiments should be performed in order for an assay to be considered safe and reliable for use in patient care?

II.      Is immunohistochemistry reliable for screening for ALK translocations?

8.   When screening for ALK translocations, does IHC provide equivalent clinical

performance characteristics when compared to FISH and RNA/DNA sequencing methods for ALK translocations?

9.   When considering IHC antibodies for screening of ALK translocations, is there a difference in clinical performance characteristics for ALK1, 5A4, or D5F3 antibodies and/or detection platforms?

10. When comparing IHC techniques for screening of ALK translocations, do any emerging techniques (anchored PCR, ultrasensitive detection systems) provide superior clinical performance characteristics?

11. If potential ALK translocations are detected in patients by a sensitive IHC assay, are the clinical performance characteristic sufficient, or does the ALK translocation need to be confirmed by an orthogonal method?

III.      In patients who are undergoing treatment with targeted tyrosine kinase inhibitors, what are the types and rates of secondary resistance?

11. Does pre-treatment discovery of de novo resistance-related mutations improve clinical outcomes?

12. Does evaluation of rebiopsy specimen improve clinical outcomes?

13. When assessing the resistance-related mutations, what are the clinical performance characteristics of the emerging technologies, including rebiopsy, NGS, and circulating DNA/CTC?

IV.      What are the clinical performance characteristics of circulating DNA/CTC in plasma when used for diagnosis of primary lung adenocarcinoma or relapse?

V.      Are there biomarkers that are predictive of clinical outcome in squamous and small cell carcinomas?

Demographic and Clinical Characteristics

•     Age

•     Sex

•     Ethnicity

•     Smoking history

•     Current smoking status

•     Histology

•     Tumor differentiation

•     Pathologic diagnosis

Clinical Validation Outcomes:

•     Treatment response rate

•     Time to progression

•     Biomarker status

•     Benefit from personalized therapy (correlation between mutation and benefit from targeted therapy)

Clinical Performance Characteristics Outcomes:

•     Accuracy

•     Specificity and sensitivity

•     Sensitivity limit/analytic sensitivity

•     Positive predictive value (PPV) and negative predictive value (NPV)

•     False positive, true positive, false negative, true negative rates

•     Turnaround time (TAT)

•     Concordance across platforms

•     Spectrum and percent of mutations detected/Types of mutations detected

Technical Validation Outcomes:

•     Types of tissue samples

•     Fixatives used

•     Analytic sensitivity and specificity

•     Reproducibility of analytic process

•     Accuracy of results

•     Assessment for relevant mutations or rearrangements

•     Use of appropriate controls

•     Sensitivity of detection system/method