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Insights From ESMO Congress 2019: Osimertinib in Non-Small Cell Lung Cancer |
Practice Community
New Haven, Connecticut
Practice Niche
Lung Cancer
Hospital and Institutional Affiliations
Chief of Medical Oncology, Yale Cancer Center and Smilow Cancer Hospital
Question In the FLAURA trial, osimertinib provided a statistically significant and clinically meaningful improvement in overall survival vs a comparator EGFR-TKI in the frontline setting in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC). What is the significance of not requiring magnetic resonance imaging (MRI) upon enrollment of a study like this, and how could that requirement have likely influenced the study findings in FLAURA? |
Answer While MRI was not required, meaning some brain metastases might have been preexisting, I believe the data still support the fact that osimertinib is having an effect. |
Question In your practice/experience, how many lines of tyrosine kinase inhibitor (TKI) therapy do patients with EGFR-mutated disease typically get, and how is this number of therapies likely relevant in the scope of the FLAURA trial? |
Answer In my practice, patients with EGFR-mutated disease typically get 1 line of TKI therapy. Now, there is some thought on giving a second-line TKI if they are resistant with a C797S mutation. This is a big question now: whether to treat with osimertinib like in FLAURA or use a first- or second-generation TKI followed by osimertinib at resistance. |
Question Researchers found that circulating tumor DNA (ctDNA) monitoring may allow for earlier identification of patients who may progress on first-line EGFR-TKI therapy, and in the detection of EGFR-mediated resistance. What are some limitations of ctDNA analysis in the setting of NSCLC? |
Answer One of the possible limitations is the sensitivity of ctDNA. Is there enough disease for [the test] to pick it up? Certainly if you have metastatic disease and enough blood that the test picks it up, that could provide very early evidence that you should start a new therapy. We are seeing more and more studies using ctDNA in that way. I’m supportive of that but I don’t know that it is a standard of care right now. |
Question Patients with certain mutations may not see an overall survival benefit from osimertinib (ie, Exon21 L858R EGFR mutations), and those with other distinct mutations (ie, TP53 exon 8 mutations) demonstrated primary resistance to frontline osimertinib. Should gene sequencing precede osimertinib administration in the frontline setting, then? |
Answer Gene sequencing prior to osimertinib in the frontline setting is the standard of care. That is how we would know someone has an EGFR mutation. There are currently no known mutations in exon 19 or 21 that would exclude a patient from the use of osimertinib. |
Question What are some comutations of EGFR that you have seen at diagnosis in your patients with lung cancer, and how could these comutations affect treatment selection? |
Answer Some of the commonly occurring comutations with EGFR are C797S or cMET; sometimes the patient develops small cell lung cancer. |