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Updated Guidelines for Molecular Testing and Targeted Therapies in Lung Cancer


The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) have followed up their 2013 evidence-based guideline with the UPDATED MOLECULAR TESTING GUIDELINE FOR THE SELECTION OF LUNG CANCER PATIENTS FOR TREATMENT WITH TARGETED TYROSINE KINASE INHIBITORS. The new guideline continues to set evidence-based standards for clinical molecular testing of non-small cell lung cancers (NSCLC) that effectively guides targeted therapy and treatment.

Rapid advancements in the understanding of lung cancer, and corresponding growth in available molecularly-targeted therapies, make this guideline revision essential to guide optimal patient care. NSCLC patients whose tumors harbor specific molecular alterations may be candidates for targeted tyrosine kinase inhibitor therapy, which may improve survival and quality of life.

The updated guideline strengthens or reaffirms the majority of 2013 RECOMMENDATIONS for patients with lung adenocarcinoma, and it also recommends testing for some new genes. Most notably, the guideline provides answers to these important clinical questions:

  • Which new genes should be tested for lung cancer patients?

  • What methods should be used to perform molecular testing?

  • Is molecular testing appropriate for lung cancers that do not have an adenocarcinoma component?

  • What testing is indicated for patients with targetable mutations who have relapsed on targeted therapy?

  • What is the role of testing for circulating cell-free DNA for lung cancer patients?

Patients battling lung cancer will benefit as their clinicians review and adopt this guideline. Stakeholders around the world are encouraged to review the guideline and implement recommendations.

From the IASLC, the updated guideline strengthens or reaffirms the majority of the 2013 recommendations for patients with lung adenocarcinoma, and also recommends testing for some new genes. Most notably:

  • Testing for ROS1 mutations is new and strongly recommended for all lung cancer patients regardless of clinical characteristics.

  • Multiplexed genetic sequencing panels (e.g., NGS testing) are preferred over multiple single-gene tests to identify other treatment options beyond EGFR, ALK, and ROS1, however single gene assays are still acceptable.

  • When NGS is performed, several other genes are also recommended – BRAF, ERBB2, MET, RET, and KRAS. However, these genes are not essential when only single gene tests are performed. Note: BRAF had late-breaking early evidence, which we expect to mature to a stronger recommendation for inclusion as a single gene assay, as well, in the near future.

  • Testing in relapse is required for EGFR (T790M), but not for ALK, as the differential sensitivities of second-line ALK inhibitors in the setting of specific acquired mutations in ALK has not yet sufficiently matured and is still investigational.

  • Testing for EGFR T790M in relapse may be done by biopsy or cell-free circulating DNA. However cell-free DNA is not appropriate for initial diagnosis at this time, unless a tissue or cytology sample cannot be obtained.

  • Previous recommendations, otherwise, were largely reinforced, with some strengthening of evidence that has led to strengthening of the original recommendations. Most notable changes:

  • Inclusion of IHC for ALK as an alternative to FISH;

  • Inclusion of any cytology sample with adequate cancer content, as opposed to recommending cell blocks.

  • Opinion is expressed that samples should also be set aside for assays to predict response to immunotherapy (e.g., PD-L1 IHC), but no specific recommendations about how to predict this treatment response were made, and will be the subject of an upcoming guideline.

The complete guideline is available online at the Archives of Pathology & Laboratory Medicine, Journal of Thoracic Oncology, and the Journal of Molecular Diagnostics.

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