The American Society of Clinical Oncology (ASCO) has endorsed a College of American Pathologists/International Society for the Study of Lung Cancer/Association of Molecular Pathologists guideline on molecular testing for patients with lung cancer.
The guidelines were published in the 13th October issue of the Journal of Clinical Oncology, the official ASCO journal, and recommends EGFR and ALK testing for all patients with lung adenocarcinoma or mixed histology with an adenocarcinoma component.
In this new guideline, the authors advice testing should be offered at the time of diagnosis to patients with advanced disease or recurrence, independent of tumor size or patient characteristics, such as gender, race, and smoking status.
The guideline aimed to answer five crucial questions: When should molecular testing be performed? How should EGFR testing be performed? How should ALK testing be performed? Should other genes be routinely tested in lung adenocarcinoma? How should molecular testing be implemented and operationalized?
No specific testing platform was identified, however the authors advised against the use of immunohistochemistry (IHC) testing for EGFR, EGFR copy number analysis, and ALK real-time polymerase chain reaction. Furthermore, rearrangements in ROS1 and RET have been identified as potential markers for testing.
“This guideline is incredibly important, as it increases the ability to personalize lung cancer care and improve outcomes for patients with advanced lung cancer,” co-chair of ASCO’s Expert Panel that endorsed the guideline Natasha B. Leighl, MD, MMSc, from Princess Margaret Hospital, said in an ASCO press release. “It describes the current evidence and helps oncologists and pathologists understand and put molecular testing into clinical practice.”
Laboratories preforming clinical tests should have a minimal cellularity requirement to enable assay validation for EGFR testing, in order to allow EGFR mutation’s detection in samples with >10% of tumor cells. Furthermore, when dealing with EGFR T790M mutation detection, testing methods should be sensitive enough to allow testing samples with >5% of tumor cells.
ALK-specific FISH assay has been approved by the U.S. Food and Drug Administration (FDA), as a prerequisite for treatment with ALK inhibitors for patients with non-small cell lung cancer. Nonetheless, evidence has been gathered that indicates IHC can be used to test for ALK-positive samples. This led the ASCO panel to decide that IHC assays using the antibodies D5F3 and 5A4 could be utilized prior to FISH testing for the detection of ALK.
KRAS mutation testing to determine if a patient is eligible for an EGFR-targeted therapy was not recommended, however, it could be used to exclude samples from requiring EGFR and ALK testing.
“This guideline will help standardize which patients are tested and when and how the testing is implemented. We hope that it will encourage testing and treatment based on molecular results”, co-chair of ASCO’s Expert Panel that endorsed the guideline Natasha Rekhtman, MD, PhD, from Memorial Sloan Kettering Cancer Center, concluded in the press release.