This program, sponsored by AstraZeneca, will allow all completely resected (R0) stage IB to stage IIIA NSCLC patients to be tested for mutations in the epidermal growth factor receptor (EGFR) gene. Pathologists and other qualified care providers may order this test reflexively on stage IB to stage IIIA resected specimens. Test results are expected to be available in 10 days or less post specimen receipt, barring exceptional circumstances.
Patients identified with either exon 19 deletions or exon 21 (L858R) substitutions may be eligible for TAGRISSO (osimertinib), as per the recent notice of compliance (NOC) by Health Canada for EGFR mutation-positive NSCLC in the adjuvant setting2, based on the evidence of the ADAURA clinical trial3. Note that changes other than EGFR L858R and exon 19 deletion might contribute to increased or decreased sensitivity to EGFR inhibition and should be interpreted accordingly. Patients with these less common alterations are not eligible for osimertinib in the context of ALTER but the information will be also valuable for treatment planning.
How will EGFR variants be detected in project ALTER?
Testing for EGFR variants will be performed using the Idylla™ EGFR test on FFPE tissue which has been specifically designed to detect the most common variants in EGFR at the stated limit of detection (LOD) including:
• G719A/C/S (LOD = 10%)
• Various exon 19 deletions (LOD = 5%)
• L858R (LOD = 5%)
• T790M (LOD = 5%)
• Various exon 20 insertions/duplications (LOD = 5%)
• L861Q (LOD = 5%)
• S768I (LOD = 5%)
How is the test ordered?
Use our ALTER requisition
What will the common results be and how should these be interpreted?
• Positive – One or more EGFR variants were detected. A list of EGFR TKI therapies approved by Health Canada and/or that have clinical evidence of efficacy will be provided based on the EGFR variant(s) identified in the clinical report. Note that only cases with EGFR exon 19 deletion and L858R mutation are eligible for osimertinib in the context of ALTER. However, information on the other EGFR alterations will also inform on treatment decision.
• Negative – No EGFR variants were detected with the Idylla™ EGFR Mutation test.
• Fail – The Idylla™ EGFR Mutation test did not provide interpretable results. The most common reasons for this being the quantity and/or quality of DNA was insufficient to obtain a result from the tests or due to a cartridge/instrument failure.
How can I access the clinical report results of an Idylla EGFR Mutation test for my patient?
• The report will be generated using the CGL SHIRE platform that has formed the basis of all CGL molecular reporting and will be uploaded in the BC Cancer CAIS database.
• The ordering pathologist and care providers will receive an email if the sample is POSITIVE for EGFR alterations.
• The integrated adoption of these two approaches will ensure optimal dissemination of test information to the vast majority of cancer physicians, internal and external to the BC Cancer system, in BC.
- Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010 Jun;17(6):1471-4. doi: 10.1245/s10434-010-0985-4. PMID: 20180029.
- Health Canada Tagrisso Product Monograph: https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=94310
- Wu Y, Tsuboi M. He J. et al. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med 2020; 383:1711-1723 DOI: 10.1056/NEJMoa2027071