Osimertinib For Uncommon EGFR Mutations in NSCLC

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Sai-Hong Ignatius Ou, MD, PhD: There are 2 common activating EGFR mutations: Deletion 19 and L858R mutations. Overall, they consist of about 90% of all activating EGFR mutations. There are 3 uncommon mutations. They constitute about 5% to 10% of the activating EGFR mutations depending on the study series. We participated in the afatinib study and LUX-Lung 2 study. Afatinib has demonstrated clinical activity in these uncommon mutations based on the LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6 studies, combined. We were part of the authorship for afatinib in the Lancet Oncology. Based on this study, the FDA approved afatinib for use in patients with uncommon mutations.

Right now, afatinib is the only EGFR TKI [tyrosine kinase inhibitor] approved for the treatment of the 3 uncommon EGFR mutations, which consist of about 5% to 10% of all activating EGFR mutations. Afatinib has comparable clinical activity in these 3 uncommon mutations, as it does with the 2 common activating mutations. However, afatinib has adverse effects such as rash and diarrhea. I think the very important question is, can osimertinib also overcome these 3 uncommon mutations because of their tolerability?

At the 2018 World Conference on Lung Cancer there was an abstract that showed that osimertinib has a very good overall response rate against all 3 of these uncommon mutations. If the overall response rates are confirmed, this actually provides us with another excellent treatment option for these patients. Because of the tolerability of osimertinib, we may actually switch to osimertinib as a first-line treatment option for these patients.

Hopefully there will be an FDA approval, but in the United States, based on this data, we may try to use this off-label for patients with these 3 uncommon mutations. They are rare. I will think about using osimertinib, but I think the standard of care will still be afatinib. That will still be the first-line treatment. But, if there are more data and the data turn out to be confirmed, or are positive, osimertinib will likely become the frontline treatment for the 3 uncommon mutations too.

Transcript Edited for Clarity