ADAURA Phase III Trial Data: Practice Changing?

Roy S. Herbst, MD, PhD: If approved in the adjuvant setting, osimertinib would be used, and then some patients would progress still. No drug is perfect, and resistance does develop to EGFR inhibitors. That would then require more research to find drugs that work in the more resistant settings. Some of these patients might end up getting chemotherapy, maybe combinations of targeted therapies. Often, recurrence with an EGFR inhibitor is seen with a c-MET amplification, so that, EGFR receptor amplification, maybe even immunotherapy finds its way into the EGFR setting. There are some data to suggest that some of the combinations, such as bevacizumab plus atezolizumab with chemotherapy, work in EGFR-mutated patients, so there are a lot of possibilities.

Based on these data, I think testing should be done in all patients, everyone with lung cancer and certainly nonsquamous cell carcinomas. But I would say because of some of the crossover, everyone with non-small cell lung cancer should have molecular profiling these days—not just for EGFR, but for the other 8, 9 molecular abnormalities that we can study. Certainly, in the early stage setting, these ADAURA data suggest that we need to know at the time of surgery who has EGFR or not because of this treatment paradigm.

There is going to be a trial, NeoADAURA, that will look at neoadjuvant EGFR. There's also going to be a trial, LAURA, which is going to be in patients with stage III disease in the adjuvant setting as well. It is very exciting to have these tools that can be used help patients with lung cancer to live longer with better quality of life.

I think for community oncologists, it's important to molecularly test your patients. We want to personalize therapy. It's been 23 years since EGFR inhibitors were first put into practice. It was 7 years before we even knew about EGFR mutations. Now we know. We also know about ALK, ROS1, NTRK, RET, c-MET, exon 14 skipping, to name a few. You want to try to know all this so that you can give the patient the best option and the best drug.

What we're seeing from ADAURA is that you want to know about it as early as possible, so that at every treatment juncture, we can discuss with the patient the best options in a shared decision-making format. Certainly, if you have a targeted therapy that has great response rates, why not use that as opposed to chemotherapy, which has much lesser rates and more toxicity? These are many more weapons for us as oncologists, myself included, to use as we treat our patients in the clinic.These oral agents are very nice, too, in these times when we know chemotherapy is a risk factor for patients, should they develop COVID-19 [coronavirus disease 2019].

Transcript edited for clarity.