Approaching a Case of EGFR+ Non-Small Cell Lung Cancer

Mark Socinski, MD:In this case, we have a 66-year-old woman who presents with symptomatic CNS disease. Although her symptoms were mild, she was found to have metastatic disease involving the brain that was relatively limited but causing symptoms. She did have a lung mass that was biopsied and did show an adenocarcinoma. She was a never-smoking Asian female; that would be the typical histology. Upon molecular interrogation, she was found to have anEGFRexon 19 deletion mutation, which is highly sensitive to EGFR TKIs. I would have treated her with steroids, and oftentimes you can make some headway in relieving the symptoms of headache and visual disturbances. If she got better with steroids, I think the question is which EGFR TKI you would use in this setting. In this setting, given the recent data from the FLAURA trial, I would recommend the use of osimertinib, which is how this patient was treated.

At this point, the brain MRI was positive for disease and had a typical appearance. That diagnosis is stage 4 disease. I don’t think you necessarily need to do a PET scan. A bone scan might be of interest because there may be a role for bone-targeting agents if she does have bone involvement. But again, I think you have here a very good therapy and I don’t necessarily think that any other tests are absolutely indicated, although there are situations where it would be reasonable to do a bone scan. In this case, I probably would not do a PET scan. I don’t know what information it would give that would be helpful over what we already have.

In a perfect world, I would like a full battery of molecular testing. There are about 7 or 8 things I would like to know about. The most common actionable driver mutation we see isEGFR. Hopefully you get that information right from the initial diagnostic material. You should be able to get that information within 1 to 2 weeks of the initial biopsy: That’s often the timeframe that we see these patients. You can buy some time, in this case, if she responds to steroids with regard to her CNS symptoms. We always say that the diagnosis of lung cancer is almost always an emotional emergency, that it’s rarely a medical emergency. I think that you have time to gather the information from the full molecular diagnostic panel and make the right decision. I counsel patients and say, “Let me do my job. Let me find out if you have any molecular alterations.” I would argue in a patient like this, particularly a never-smoking Asian female, that the likelihood you’re going to find an oncogenic driver is 60% or more, possibly. So, you’re more likely to find an oncogenic driver in a patient like this, and I would try to temporize things with steroid treatment and rush the molecular testing as quickly as I can. In this case, we obviously know she hit the target of having anEGFRexon 19 deletion mutation.

Again, this patient has stage 4 disease. We don’t think that we cure these patients. But a patient like this, with anEGFRexon 19 deletion mutation, has a much better prognosis than the average lung cancer patient. These patients live for years. The average patient may live for 3, 4, or 5 years, if not longer, with proper therapy, which in this case is an EGFR TKI. Her prognosis is much better than average. I tell these patients not to read information about lung cancer on the internet because a lot of it can be misleading. These patients need to understand that this is a different type of lung cancer. This is driven by an oncogenic driver, which is highly targetable with effective oral therapy in this setting.

Transcript edited for clarity.

December 2017

• A 66-year-old Asian woman presents to her PCP complaining of visual disturbances, nausea, fatigue, and sporadic headaches
• History: HTN, managed on candesartan; hyperlipidemia managed on simvastatin; no smoking history
• PE: BP, 148/70; LLL auscultation reveals decreased breath sounds
• CBC: WNL
• Imaging studies:
  • MRI of the head demonstrated a right parietal mass at the gray—white junction with vasogenic edema
  • CT of chest, abdomen, and pelvis revealed a 3.4-cm mass in the left lower lobe, and several small liver nodules
• CT-guided transthoracic needle biopsy of the lung lesion showed grade 2 adenocarcinoma, acinar
• Molecular testing: EGFR exon 19 deletion
• Staging: T2aN0M1c
• ECOG 1
• The patient was started on osimertinib 80 mg once daily