To establish evidence-based recommendations for the molecular analysis of lung cancers
that are that are required to guide EGFR- and ALK-directed therapies, addressing which
patients and samples should be tested, and when and how testing should be performed.
Three cochairs without conflicts of interest were selected, one from each of the 3
sponsoring professional societies: College of American Pathologists, International
Association for the Study of Lung Cancer, and Association for Molecular Pathology.
Writing and advisory panels were constituted from additional experts from these societies.
Three unbiased literature searches of electronic databases were performed to capture
articles published published from January 2004 through February 2012, yielding 1533
articles whose abstracts were screened to identify 521 pertinent articles that were
then reviewed in detail for their relevance to the recommendations. Evidence was formally
graded for each recommendation.
Initial recommendations were formulated by the cochairs and panel members at a public
meeting. Each guideline section was assigned to at least 2 panelists. Drafts were
circulated to the writing panel (version 1), advisory panel (version 2), and the public
(version 3) before submission (version 4).
The 37 guideline items address 14 subjects, including 15 recommendations (evidence
grade A/B). The major recommendations are to use testing for EGFR mutations and ALK
fusions to guide patient selection for therapy with an epidermal growth factor receptor
(EGFR) or anaplastic lymphoma kinase (ALK) inhibitor, respectively, in all patients
with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other
clinical risk factors, and to prioritize EGFR and ALK testing over other molecular
predictive tests. As scientific discoveries and clinical practice outpace the completion
of randomized clinical trials, evidence-based guidelines developed by expert practitioners
are vital for communicating emerging clinical standards. Already, new treatments targeting
genetic alterations in other, less common driver oncogenes are being evaluated in
lung cancer, and testing for these may be addressed in future versions of these guidelines.