Genotyping: Looking at the Future of Lung Cancer Care

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BOSTON—As more targeted therapies for non–small-cell lung cancer (NSCLC) become available, experts are assessing which patients’ tumors should be genotyped and when. Although genotyping—not to be confused with genetic testing—is becoming increasingly important in developing a treatment plan, professional guidelines do not yet recommend incorporating it as a routine part of care for patients with NSCLC.


Whether to test prior to initiating therapy depends on each patient’s clinical situation, according to Michele Myers, BSN, RN, OCN. “I would recommend that patients who have a lifelong history of being a never-smoker, as well as patients with a light smoking history (<10 pack-years) have their tumors genotype tested,” Myers, who is a thoracic access nurse at Massachusetts General Hospital (MGH) in Boston, told The Oncology Nurse-APN/PA.


In April, the American Society of Clinical Oncology issued a provisional clinical opinion (PCO) recommending genotype testing in patients with advanced NSCLC if first-line therapy with an epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor is being considered. Studies show that EGFR inhibitors gefitinib (Iressa) and erlotinib (Tarceva) are less effective in patients with NSCLC who do not have EGFR mutations. Myers hailed the PCO as a positive step for patients. “My hope is that those patients, especially in the community setting, will now have the same access to genotyping as those patients who are seen and treated in a tertiary care setting.”


The most common mutations in NSCLC include HER2, P1K3CA, EGFR,MET, PDGFR, BRAF, ALK, and KRAS, according toLecia V. Sequist, MD, MP, with MGH’s thoracic division and assistant professor of medicine at Harvard Medical School. More than one-quarter of patients have none of these, suggesting many more mutations await discovery. Although studies show erlotinib is effective in EGFR-positive NSCLC, it is not approved for the first-line setting. Sequist said the Iressa Pan-Asia Study (IPASS), which compared gefitinib with chemotherapy in NSCLC, showed that EGFR-positive patients had longer progression-free survival and better symptom control and quality of life when treated with gefitinib. Gefitinib is not readily available in the United States and not approved for general use in patients with NSCLC.


Crizotinib is another promising targeted therapy and, if approved by the US Food and Drug Administration, will be indicated for the 2% to 5% of NSCLC patients with an EML4-ALK translocation. Other targeted agents under evaluation in NSCLC include PLX4032, PF02341066, BEZ235, afatinib, and imatinib.


Nursing education does not adequately prepare nurses for the transformation under way in how lung cancer is treated. “Nurses right now in general practice are used to the typical drug treatments that are chosen based on where in the body the cancer is found,” said Myers. “Going forward, nurses will need to have a basic understanding of what genotype tumor-tissue testing entails and how this could benefit their cancer patients.” She added that providing general education on which patients with cancer should be tested, along with how and when, and how to use those results “will allow oncology nurses to advocate and participate in decisions and discussions for their cancer patients.”


Some larger institutions, such as MGH, already genotype tumors in all patients with newly diagnosed NSCLC. MGH uses its custom SNAPSHOT panel for analyzing a core biopsy sample of tumor tissue. “SNAPSHOT provides information on 110 different mutations involving 13 different genes,” Myers said. “Once we know the genetic profile of a patient’s lung cancer, we can then pair the patient with the best targeted therapy for their cancer,” she explained.


Different degrees of testing are available commercially and through tertiary care centers, yet “patients can face many different obstacles in getting the tissue genotype tested,” said Myers. Commercial testing for EGFR, KRAS, and ALK mutations is available but requires patients to follow up with the local oncologist to determine eligibility for a targeted therapy. For much broader “package” testing at tertiary care centers, it is incumbent on patients to locate centers that provide the testing.


Last fall, a 2-year lung cancer mutation consortium was launched at 14 sites around the country. Myers said these institutions are providing free testing to patients with advanced lung adenocarcinoma with the genotyping protocol developed at MGH, to identify 10 genetic mutations. “Patients will then be referred to the appropriate clinical trial or therapies based on the individual molecular profile results,” she said.

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