Personalizing Therapy for EGFR Exon 20-Mutant NSCLC

Transcript:John Heymach, MD, PhD: EGFR exon 20 mutations are usually detected by a couple of different means. There’s next-generation sequencing. Panels like Foundation Medicine, for example, or Oncomine are 2 common ones. Or liquid biopsies can be used. Here, circulating tumor DNA is used to identify exon 20, either EGFR or HER2. In our study, right now, either Guardant360, cobas, or the therascreen assay can be used to identify EGFR exon 20. For HER2 exon 20, the Guardant360 assay is used as one of the eligibility criteria as part of the study. So, we’ve really left things open. A variety of different methods can be used to detect exon 20.

I’ll point out that exon 20 EGFR and HER2 are mutations that had not really been screened for, routinely, in the past. The rise of next-generation sequencing, things like circulating tumor DNA assays, like Guardant360, and next-generation panels, like Foundation Medicine and Oncomine, are really uncovering a lot more of these mutations that weren’t really assessed in the past. Before, standard criteria for a lung cancer patient would just be EGFR and ALK. Some people looked for ROS and BRAF. This really illustrates the importance of looking much more broadly, for all of these different mutations. Now we’ve got drugs that could be active for them.

I think the case of EGFR illustrates that as cancer therapies move further along, we’re targeting smaller and smaller subgroups of patients that have particular mutations. In essence, our diseases are becoming more personalized. If you look at lung cancer and EGFR mutations as a whole, it’s not surprising that the initial drugs were focused on the biggest populations—those with classical mutations like exon 19 deletions and L858R. But other patients had these other mutations. And so, I think we’re entering a very exciting era, where we’re developing specific drugs for these other specific mutations.

As more patients get next-generation sequencing, or liquid biopsies, and these broader panels, more of these rare mutations are going to become uncovered. It will be feasible to test a lot of these new drugs that are coming along. So, really, these 2 things go hand in hand: the development of drugs that target these smaller subgroups that have particular mutations and the arrival of next-generation sequencing or liquid biopsies, where we can identify these mutations that we previously weren’t identifying. It’s a very exciting time for cancer therapy. Not just for lung cancer, but for all cancers as a whole.

Transcript Edited for Clarity