Suresh S. Ramalingam, MD
The National Comprehensive Cancer Network (NCCN) unveiled its latest treatment guidelines for patients with varying histologies of non–small cell cancer (NSCLC), including those who are EGFR
One of the notable updates in this area, explained Suresh A. Ramalingam, MD, is the category 2A recommendation to give osimertinib (Tagrisso), a third-generation irreversible EGFR inhibitor designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, in the first-line setting for patients whose disease is EGFR
-mutation–positive disease, and how the frontline recommendation of osimertinib will impact clinical practice.
OncLive: Regarding EGFR-mutant NSCLC, what are the most notable updates to the NCCN guidelines?
: The most important update is the introduction of osimertinib in the frontline space, and that follows the FLAURA data that we presented at the 2017 ESMO Congress a couple of months ago. That study compared osimertinib to erlotinib or gefitinib for first-line therapy in patients with either exon 19 and 21 alterations. That study showed superiority for osimertinib; the median PFS was improved from 10.2 months [with standard therapy] to 18.9 months. The hazard ratio was 0.46.
We also saw that osimertinib had activity in the brain more so than the other 2 drugs. Based on that, the trial announced that osimertinib was superior to current standard-of-care TKIs in the first- line setting. The NCCN guidelines follow the results of the trial to recommend osimertinib as an option in the first-line space.
The guidelines emphasize testing for EGFR/ALK/ROS1. How can the results of these tests guide physician’s choice of therapy?
We now know that for every patient with nonsquamous NSCLC, molecular testing is critical even before we start treatment for advanced-stage disease. EGFR exon 19 and 21 alterations are associated with high sensitivity to EGFR inhibition. I believe patients should have testing for EGFR mutations, BRAF mutations, ALK translocations, and ROS1 translocations before they start therapy. Those are the 4 oncogenes where there is a proven therapy available for patients with those abnormalities.
The other thing is regarding tissue-based testing. For EGFR, plasma testing is now an option if tissue is not available. If the plasma testing reveals that the patient has exon 19 or 21 alterations, then they can also derive benefit from EGFR TKI therapy. That is another option that has emerged now in the field.
What is the significance of osimertinib now being recommendation as a therapeutic option in the frontline setting for EGFR-mutant patients?
In the United States, these data clearly show that osimertinib is superior to current therapies. It is safer from a toxicity standpoint, and it has benefits when it comes to activity against brain metastases. For these reasons, I believe osimertinib will be a preferred first-line therapy for EGFR
If the NCCN recommends giving osimertinib in the first-line setting, what is the optimal second-line option for those who progress on the third-generation EGFR inhibitor?
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