On Cancer: Lung Cancer Patients Will Benefit from New Molecular Testing Guideline

In recent years, rapid advances in clarifying the molecular underpinnings of lung cancer have led to more-personalized medical treatments for people with the disease, the leading cause of death from cancer in the United States. Today, doctors can analyze a patient’s tumor for specific genetic abnormalities to determine which targeted therapies are likely to be beneficial. 

Despite the availability of these tests and treatments, a significant portion of lung cancer patients around the country do not have their tumors analyzed upon diagnosis, due partly to confusion among many doctors over which patients would benefit.

Now three leading health organizations have jointly issued a guideline establishing clear standards regarding tests for two common genetic abnormalities linked to lung adenocarcinoma, the most common type of lung cancer. The guideline recommends that all patients with advanced lung adenocarcinoma should be tested for abnormalities in two specific genes, EGFR and ALK, regardless of clinical variables such as sex, race, or smoking history.

“This guideline establishes what we consider to be the minimum level of genetic testing for any patient diagnosed with lung adenocarcinoma,” says Memorial Sloan-Kettering molecular pathologist Marc Ladanyi, one of three co-chairs of the international expert panel that developed the guideline. “We hope this guideline will be used by doctors nationally and globally, making it standard practice for lung cancer patients to receive the most-essential molecular testing of their tumors.”

Significant Patient Population

Approximately 20 to 25 percent of patients with lung adenocarcinoma are thought to have one of these two genetic abnormalities in their tumor, and targeted therapies already exist for both types. The abnormalities are both more commonly found in lung cancers from people who never smoked but also arise in smokers.

Patients with an EGFR abnormality in their lung cancer can be treated with the drug erlotinib (Tarceva^®), while people whose lung tumors contain an ALK abnormality can receive crizotinib (Xalkori^®). In addition, new drugs targeting these disease pathways are being tested in clinical trials.

As co-chair, Dr. Ladanyi represented the International Association for the Study of Lung Cancer (IASLC), which drew up the recommendations in collaboration with the College of American Pathologists and the Association for Molecular Pathology. Dr. Ladanyi was asked to serve as the IASLC’s co-chair because of Memorial Sloan-Kettering’s widely recognized expertise in molecular testing of lung cancer.

The guidelines are published this week in three journals — Archives of Pathology & Laboratory Medicine, the Journal of Thoracic Oncology, and the Journal of Molecular Diagnostics.

The Rapid Rise of Molecular Testing

The new guideline reflects the growing importance of genetic biomarkers in the diagnosis and treatment of cancer.   

“Even today, some oncologists might say, ‘This person is a smoker. It’s not worth testing for EGFR and ALK mutations,’— which is not correct,” Dr. Ladanyi explains. “We want to make clear that just using clinical parameters to select patients for genetic testing is no longer medically acceptable.”

In addition to advocating testing for EGFR and ALK mutations, the guideline sets standards for the methods by which tumor samples are tested and how quickly results should be made available by the laboratory so the oncologist can make treatment decisions.

Impact on Treatment

Memorial Sloan-Kettering has tested for the EGFR mutations since 2004 and for the ALK abnormality since 2009 and continues testing all lung cancer patients for these and other mutations as part of the initial workup of patients with lung cancer.

“Using molecular testing, we’re able to guide treatment for a significant proportion of patients in a way we never could before,” says Memorial Sloan Kettering medical oncologist Gregory J. Riely. “This testing lets us select drugs that are going to work better and longer than standard chemotherapy, often with less toxic side effects.”

Dr. Riely believes the guideline will help ensure that routine testing is adopted by oncologists everywhere.

“I think the release of the guideline is a major step forward for advancing personalized medicine throughout the world,” he says. “It sets a minimal bar, explains the standard of care for patients with lung cancer, and helps to identify the key factors that help us pick drugs for patients today.”

Dr. Ladanyi says that continued research identifying new molecular biomarkers will require that the guideline be regularly revisited and revised, possibly as often as once a year, because the pace of discovery is so swift. The guideline was developed based on studies that were already published, so many ongoing studies and clinical trials could not be included but will soon produce new information that needs to be incorporated.

For now at least, the guideline establishes an unequivocal standard that doctors diagnosing and treating lung cancer will be expected to follow. “Ultimately, doctors who are not testing all lung adenocarcinoma tumors will have to justify why they are deviating from the guideline,” Dr. Ladanyi says.