EGFR Exon 20 Insertion As A Therapeutic Target in Non-small Cell Lung Cancer - Episode 7

Unmet Needs and Future Directions

Zofia Piotrowska, MD, discusses unmet needs, novel treatment strategies and future perspectives for patients with EGFR exon 20-positive NSCLC.

Matthew Fowler: What are some remaining unmet needs in this patient population?

Zofia Piotrowska, MD: It’s great to see the progress that we’ve made, but there are still many unmet needs in this patient population. We can say that the efficacy results that we’re seeing are great, but they’re still far from the high rates of responses that we’re used to seeing, for example, with osimertinib in the more common types of EGFR mutations like exon 19 deletion or L858R. Even more effective therapies would be great. We’ve also seen some toxicities with these agents, including GI [gastrointestinal] and skin toxicities with mobocertinib, and infusion reactions and skin toxicities with amivantamab. Treatment options in the future that may minimize those toxicities and be even better tolerated would certainly be welcome. Acquired resistance to these agents is still an unknown, and what treatment options may be available for patients who have progressed on these options will be important to evaluate. Finally, I’ll make the point of CNS [central nervous system] metastases. Many of these patients have brain metastases, and we need better and more CNS penetrant options in the future.

Matthew Fowler: Could you talk a little about some of the ongoing trials that intrigue you and could have a strong impact on the field?

Zofia Piotrowska, MD: There are a number of new drugs in development that are trying to develop agents with a better therapeutic window. We know that many of the toxicities that we see with these agents have to do with the fact that while these drugs may inhibit the mutated EGFR and the exon 20 insertion mutated EGFR, they also have activity against wild-type EGFR, which all of us have in our skin and in our gut, and lead to some of these toxicities. There are drugs now in development that are trying to be more specific for that mutated EGFR, including DZD9008, CLN-081, a drug from Black Diamond Therapeutics, and others that are in development that have the potential to be more effective and have a better safety profile. We’re also seeing trials of combinations of these agents, or combinations of one of these agents, for example, with chemotherapy or others. We hope that that may lead to improved efficacy.

Matthew Fowler: Do you have any closing thoughts to share that we haven’t really touched on in this area?

Zofia Piotrowska, MD: It’s just an exciting time for targeted therapies in lung cancer broadly, and specifically within the field of EGFR. It’s important to close on the fact that I recognize it’s a challenge for oncologists, particularly general oncologists, to recognize these increasingly complicated next-generation sequencing [NGS] reports, to identify these mutations, and to select between the many treatment options that we have. I encourage you to carefully read these NGS reports, and if you’re not sure what a particular mutation means, reach out to either those who issued the report or to large academic centers so that we can help you ensure that you’re selecting the best treatment for your patients, explore clinical trial options that may be available, and make sure that we’re getting the best treatments to each patient.

Matthew Fowler: Thank you so much for your valuable insight.

Zofia Piotrowska, MD: Thanks for having me.

Matthew Fowler: Thank you to our audience for watching this CancerNetwork® OncView™ program from MJH Life Sciences™. We hope you found this to be valuable to your clinical practice.

Transcript edited for clarity.