Molecular Pathology Laboratory Network

Non-small-cell lung carcinoma (NSCLC) accounts for up to 80% of all lung cancers with an overall 5-year survival rate of 10% to 15%. Management of NSCLC requires a rational approach to reduce treatment cost and provide effective targeted drug therapy.

Patients now benefit from the availability of several new drugs to treat advanced and metastatic NSCLC. Eligibility for these drugs is concurrent with companion diagnostic testing.

Erlotinib and EGFR mutations

Between 10-20% of non-squamous NSCLC tumors harbor activating EGFR mutations and are sensitive to Tyrosine Kinase Inhibitors (TKI). The OPTIMAL study demonstrated patients with advanced EGFR mutation-positive NSCLC treated with first line erlotinib (Tarceva) had increased median progression free survival from 4.6 to 13.1 months.

Crizotinib and ALK gene rearrangements

The FDA has recently approved  Crizotinib (Xalkori) for treatment of patients with locally advanced or metastatic NSCLC that is ALK-positive. The ALK Break-Apart FISH Probe Kit detects rearrangement of the anaplastic lymphoma kinase (ALK) gene in NSCLC. Upto 5% of non-squamous NSCLC carry ALK gene rearrangements.

Patients negative for EGFR mutations benefit minimally from chemotherapy and are resistant to TKI's. Crizotinib blocks certain kinases including those produced by abnormal ALK gene rearrangement. A retrospective analysis by Shaw et al, published in Lancet Oncology, showed that ALK-positive NSCLC patients treated with Crizotinib did have improved, two-year survival compared with that of Crizotinib-naive controls.

NSCLC Biomarker Recommendations

Draft recommendations by College of American Pathologists (CAP) in conjunction with International Association for the Study of Lung Cancer (IASLC) and Association for Molecular Pathology (AMP) indicate that patients with advanced stage disease and an adenocarcinoma component should be tested for EGFR and ALK gene mutations within 13 days of biopsy.

Test Information and Specimen Requirements

• EGFR Gene Mutation Analysis
• ALK Gene Rearrangement

Resources

NCCN guideline NSCLC

Zhou C et al. (2011).Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncology 12:735-742

Shaw AT et al. (2011).Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol.12:1004-12