Case 4: Upfront Osimertinib in Metastatic EGFR+ NSCLC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARDBenjamin P. Levy, MD:I may have failed to mention that the patient did have a C797S mutation upon resistance that was T790M loss retention to exon 19. That’s important. So, this patient does have a C797S mutation. We’ll talk about how, as medical oncologists, we may manage what we’re finding on these biopsies, in terms of mechanisms of resistance to osimertinib.

But let’s back up a bit and talk about the patient’s treatment, upfront. Do you feel comfortable starting osimertinib in a patient with asymptomatic brain metastases, and not even sending the patient to radiation oncology?

Anne S. Tsao, MD:I absolutely do. She’s getting a little borderline with that 1.2-cm occipital mass. If it’s a large mass, I will usually do SBRT [stereotactic body radiation therapy] and then start osimertinib. I do not do whole-brain radiation therapy in these patients any more, with the availability of osimertinib.

Benjamin P. Levy, MD:Yes. Paul?

Paul K. Paik, MD:I agree. The great thing about this class of drugs and the experience that we’ve seen for CNS [central nervous system]-specific disease, and this also relates toALK-rearranged lung cancer, is that we’ve seen phenomenal responses in the brain. This really allows us to spare patients from the toxicity of whole-brain radiation therapy. It also allows us to hold off on SRS [stereotactic radiosurgery], for later on, when we may potentially need it.

Benjamin P. Levy, MD:Is there a threshold for which we think, “OK, it’s symptomatic. There is more edema.” Is there a time when we think, “OK, it’s time.”?

Anne S. Tsao, MD:It takes a little time for osimertinib to work. And so, if the tumor is quite sizable, there’s a lot of edema, and the patient is symptomatic, you don’t have a choice. You have to go with local control with SBRT. But, like I said, she’s very safe—1.2 cm being the largest mass. With theEGFRmutants, we tend to see diffuse small, subcentimeter metastases everywhere. I’m very comfortable treating those patients with osimertinib.

Transcript edited for clarity.