The Changing Landscape of Treatment for EGFR+ Lung Cancer - Episode 8

Improving the Management of EGFR+ NSCLC


Sai-Hong Ignatius Ou, MD, PhD: In summary, the approval of osimertinib as frontline treatment in EGFR-mutant lung cancer has changed the landscape of how we treat EGFR-mutant lung cancer. In the past, we gave drugs that had a fair amount of adverse effects, such as rash and diarrhea. With the introduction of osimertinib, I think the adverse effect profile issue is solved. We also have a very good progression-free survival of about 18.9 months. With the addition of the abstract that shows that osimertinib has clinical benefit in EGFR uncommon mutations, we can potentially expand the use of osimertinib to these 3 uncommon mutations. And, if the ADAURA study is positive, we may even see osimertinib used as adjuvant therapy in EGFR-mutant lung cancer.

The unmet need that we can anticipate for the future is managing resistance to osimertinib. We need to biopsy at disease progression, most likely with a liquid biopsy that may be augmented with a tissue biopsy if we don’t find any resistant mutations. Then, we will have to combine a different inhibitor with osimertinib for the specific type of resistant mutation, with the exception of small cell transformation.

Osimertinib is very well tolerated. The 80-mg dose that was selected is way below the maximum tolerated dose of 240 mg. Even if there is a drug—drug interaction, that increase in exposure of osimertinib is still very well tolerated.

Another unknown and not approved indication is for the use of osimertinib in brain metastases, and even leptomeningeal metastases. The dose that has been investigated for leptomeningeal carcinomatosis is 160 mg once a day. It’s twice the approved dose of 80 mg. Sometimes we can’t get insurance approval for the use of the 160-mg dose. We would like to see more data on CNS [central nervous system] metastases and leptomeningeal carcinomatosis so that we can use osimertinib at 160 mg for the indications. Those are, I think, the challenges that we face going forward with EGFR-mutant lung cancer. We look forward to seeing if we can get a fourth-generation EGFR TKI [tyrosine kinase inhibitor] in the future that would help patients.

Transcript Edited for Clarity