ASCO today endorsed a joint clinical practice guideline from three other entities that addresses questions about the appropriate use of EGFR-mutation and ALK-rearrangement testing in patients with lung cancer.
A key recommendation from the guideline — developed by the College of American Pathologists, the International Association for the Study of Lung Cancer and the Association for Molecular Pathology — states that clinicians should offer EGFR and ALK testing to all patients with lung adenocarcinoma, as well as those with mixed lung cancer with an adenocarcinoma component.
The testing should be offered regardless of characteristics — such as smoking status, gender and race — to help determine which patients could benefit from targeted therapy with tyrosine kinase inhibitors, according to the guideline.
“This guideline is incredibly important, as it increases the ability to personalize lung cancer care and improve outcomes for patients with advanced lung cancer,” Natasha B. Leighl, MD, MSc, medical oncologist at Princess Margaret Hospital in Toronto and co-chair of the ASCO expert panel that reviewed and endorsed the guideline, said in a press release. “It describes the current evidence and helps oncologists and pathologists understand and put molecular testing into clinical practice.”
Patients with advanced-stage disease should be offered testing at the time of diagnosis, and patients with lower-stage disease should undergo testing at the time of progression or recurrence, the guideline states.
An expert consensus encourages EGFR and ALK testing for early-stage carcinomas at diagnosis. However, in the discussion portion of the endorsement, the ASCO expert panel suggested this information will become important for informing treatment decisions at the time of recurrence, because targeted therapies are only approved in the advanced setting.
The guideline also contains recommendations about different testing methods.
“The guideline will help standardize which patients are tested, and when and how the testing is implemented,” Natasha Rekhtman, MD, PhD, a pathologist at Memorial Sloan Kettering Cancer Center and co-chair of the ASCO expert panel, said in the press release. “We hope that it will encourage testing and treatment based on molecular results.”
The recommendations state that any validated EGFR testing method with sufficient performance characteristics is appropriate; however, immunohistochemistry (IHC) for total EGFR and EGFR copy number analyses are not recommended.
Fluorescence in situ hybridization (FISH) is recommended for ALK testing, although the guidelines recommend against using reverse-transcription polymerase chain reaction. The ASCO panel also noted ALK IHC — which is recommended in the guidelines to select specimens for ALK FISH testing if carefully validated — has become a more widely used modality and shows promise as a sensitive, rapid and inexpensive assay.
The guidelines also emphasize the importance of testing validation, quality assurance and 2-week turnaround times.
Although the guidelines recommend prioritizing EGFR and ALK testing, the increasing number of other targetable molecular alterations — such as ROS1 and RET rearrangements — will become a key consideration in the effort to maximize molecular testing and personalize treatments.
“Future guidelines will be needed to address testing for these and other emerging alterations and strategies for testing of a growing number of biomarkers as they enter clinical practice, which challenges the practicality and feasibility of performing multiple separate assays for each individual alteration, particularly in limited tissue samples,” Leighl and colleagues wrote. “In this regard, recent innovations in multigene testing methodologies afford the capability of detecting multiple molecular alterations in a single assay and may hold significant promise in clinical testing.”
Disclosure: See the study for a list of the researchers’ relevant financial disclosures.