Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors

New Lung Biomarker Guideline Released January 2018 by CAP, IASLC, and AMP

AMP has again partnered with The College of American Pathologists (CAP) and the International Association for the Study of Lung Cancer (IASLC) to update and revise the 2013 evidence-based "Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors.” This 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 NSCLC, 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 (TKI) therapy, which may improve survival and quality of life.

The 2018 guideline strengthens or reaffirms of the majority of the 2013 recommendations for NSCLC patients and recommends additional molecular biomarker testing. 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. In addition to small mutations, NGS assays have the capability to detect fusions/rearrangements and copy number changes in the examined genes. NGS also enables the use of small specimens (e.g., fine needle aspirates) that are standard of care and help avoid the risks to the patient associated with obtaining surgical biopsies.
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.

AMP, CAP and IASLC collaboratively developed this evidence-based guideline, consensus statements, clinical tools and resources related to the practice of lung cancer pathology and laboratory medicine, oncology, and molecular diagnostics. Through this work, these organizations and their members continually educate stakeholders and advance the quality of diagnostic medicine to improve lung cancer patient outcomes.

An international, multi-disciplinary panel of expert authors, appointed by each of the organizations, included pathologists, oncologists, pulmonologists, a methodologist, laboratory scientists, and patient representatives, worked collaboratively to develop the guideline through an evidence-based process following Institute of Medicine standards for guideline development. Collectively, all three organizations look forward to the continuing evolution in diagnostics and care for lung cancer patients as technology, scientific understanding, and clinical practice evolve. Since these recommendations represent current best practice in a rapidly developing field, we anticipate a need for updates in the future.

Project Co-Chairs:

Philip T. Cagle, MD on behalf of CAP

Yasushi Yatabe, MD, PhD on behalf of IASLC

Neal Lindeman, MD on behalf of AMP

About the College of American Pathologists

As the world's largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs, the College of American Pathologists (CAP) serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide. For more information, READ THE CAP ANNUAL REPORT at CAP.ORG.

About the International Association for the Study of Lung Cancer

The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes more than 6,500 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis and treatment of all thoracic malignancies. Visit www.iaslc.org for more information.

About the Association for Molecular Pathology

The Association for Molecular Pathology (AMP) was founded in 1995 to provide structure and leadership to the emerging field of molecular diagnostics. AMP's 2,300+ members practice in the various disciplines of molecular diagnostics, including bioinformatics, infectious diseases, inherited conditions and oncology. They include individuals from academic and community medical centers, government, and industry; including pathologist and doctoral scientist laboratory directors; basic and translational scientists; technologists; and trainees. Through the efforts of its Board of Directors, Committees, Working Groups, and members, AMP is the primary resource for expertise, education, and collaboration in one of the fastest growing fields in healthcare. AMP members influence policy and regulation on the national and international levels, ultimately serving to advance innovation in the field and protect patient access to high quality, appropriate testing. For more information, visit www.amp.org .