ONCAlert | 2018 SGO Annual Meeting on Women’s Cancer
Lung Cancer Case Studies

Treatment Options at Relapse for EGFR-Mutated NSCLC

Roy S. Herbst, MD, PhD
Published Online:May 30, 2017
In this case-based interview, Roy Herbst, MD, PhD, discusses the treatment of a patient who develops EGFR mutant non-small cell lung cancer.

Treatment of EGFR Mutant Non-Small Cell Lung Cancer


Roy S. Herbst, MD, PhD: This is a very interesting question. When do you switch therapies with an EGFR inhibitor? My feeling is that you want to maximize your frontline EGFR inhibitor as long as possible. Of course, when to switch would depend on the patient’s symptoms and the options you have next. So, if this is a patient who’s beginning to progress but it’s a slow progression—there are few symptoms—I would do a few things. I would probably try to keep the EGFR inhibitor going for as long as possible.
 
Tumors are polyclonal, and, of course, there could be a resistant population and a sensitive population. With time, of course, under the selection pressure of a first-line EGFR agent, we will move more towards the resistant population. But I would try to keep the frontline drug going for as long as possible. I would, at some point—when it became convenient, when there’s something easy enough to biopsy—get a new biopsy, and then test it for T790M mutation, which is a secondary mutation and the most common form of resistance. So, that would be the first thing—keep the agent going as long as possible, and gain the knowledge of what the resistance mechanism is. Perhaps the patient has c-MET amplification. That’s another treatable, albeit in clinical trial, type of abnormality.
 
Then, of course, if the patient had no T790M mutation, I’d really try to keep the first-line EGFR agent going as long as possible. Because I know, if we stop that, there will be a flare, and when we go to chemotherapy, the chance of response will be 20%—maybe 25% to 30%—and it won’t go that well, even though we can do it. Of course, we could consider immunotherapy at that point. The problem is that, at least from some of the big randomized studies, patients with EGFR-mutated disease did not do that well with single-agent immunotherapy, probably because their mutational burden is low. The tumor was addicted and driven by one mutation, and that makes the patient less likely to respond.
 
Now, if the patient had a T790M mutation, the light goes off again, because that tells you that you have a patient for whom you have the next drug. Then, the question is, how long can you eek out the benefit of the frontline agent before starting a new drug? But at some point, you do want to make sure that the patient gets a new drug. Also during this period, if someone is progressing, keep an eye on the brain, because sooner or later the disease will end up there and, of course, the morbidity can be much higher.
 
My sense for this patient is to look for an EGFR mutation. If you don’t look, you won’t find it. If you have it, treat for it, even in patients with poor performance statuses. If they then recur before going to chemotherapy, do everything you can to see if they have a T790M mutation, because, if they have that secondary mutation, your chance of response would be 60% to 70%. Then, you have the ability to use a drug called osimertinib, which gets both EGFR-mutant receptors as well as the receptors for the T790M secondary mutation and is much more specific for the mutant than the wild-type receptors. So, you have far less rash and diarrhea with this drug. Keep that in mind as a treatment. And then, of course, we need to do more research into how to integrate immunotherapies and some of the other targeted therapies, whether it be for c-MET or other targets, into this setting.

Transcript edited for clarity.
 
  • 65-year-old male, former smoker (25 pack-years, quit 12 years ago) presented complaining of persistent lower back pain, extreme fatigue, shortness of breath, and a 25-lb weight loss in the past 6 months.
  • PMH includes rheumatoid arthritis which significantly limits his physical activity.
  • Back pain also limited the patient’s daily activity.
  • MRI of the spine showed evidence of multiple lesions, but none were causing cord compression.
  • CT of the chest showed a 4-cm mass in the left lung, with enlarged bilateral mediastinal lymph nodes.
  • The MRI of the brain revealed no metastases.
  • ECOG PS was assessed to be 2. 
  • He underwent an endobronchial ultrasound-directed biopsy of the mediastinal lymph nodes.
  • Pathology revealed poorly differentiated adenocarcinoma.
  • Molecular testing showed a mutation in EGFR exon19 deletion.
Publications
Copyright © TargetedOnc 2018 Intellisphere, LLC. All Rights Reserved.