EGFR Exon 20 Insertion As A Therapeutic Target in Non-small Cell Lung Cancer - Episode 1

Overview of Advanced NSCLC with EGFR Mutations Including Exon 20 Insertions

Zofia Piotrowska, MD, provides an overview of EGFR mutations in advanced NSCLC, including EGFR Exon 20 insertions, and their clinical significance in patients with advanced NSCLC.

Mathew Fowler: Hello, and welcome to this CancerNetwork® OncView program titled “EGFR Exon 20 Insertion as a Therapeutic Target in Non–Small Cell Lung Cancer.” I’m Mathew Fowler, editor with CancerNetwork®. Dr Zofia Piotrowska, an assistant professor of medicine at Harvard Medical School and a lung cancer medical oncologist at Massachusetts General Hospital. Thank you for joining us.

Could we start with a brief overview of EGFR mutations leading up to the identification of EGFR exon 20 insertion mutations as a therapeutic target?

Zofia Piotrowska, MD: This is a very important question because the landscape of EGFR mutations in non–small cell lung cancer has gotten increasingly complex in recent years. EGFR mutations were discovered in 2004. But historically, we’ve thought about these as the most common sensitizing mutations, which are EGFR exon 19 deletions and L858R point mutations. Those mutations are sensitive to many EGFR inhibitors and are commonly treated with drugs like osimertinib in the first line. But recently, we’ve identified that EGFR exon 20 insertions, which make up 5% to 10% of EGFR mutations in lung cancer, are their own unique entity. These have historically been resistant to older generations of EGFR inhibitors, and they’ve become relevant in recent years because we’ve had new and more effective therapies for patients with these mutations. It’s important not just to recognize that your patient may have an EGFR mutation on their molecular testing report, but to specifically look at which type of mutation they have and think about the implications of that specific mutation for treatment.

Mathew Fowler: What’s the clinical significance of EGFR exon 20 insertion as a target?

Zofia Piotrowska, MD: When you find an EGFR exon 20 insertion, the significance is that there are several approved therapies for patients with these mutations; therefore, it has an impact on treatment. We’re going to talk about some of those recent approvals during this program.

Mathew Fowler: Before we get there, how have the NCCN [National Comprehensive Cancer Network] Guidelines been updated to recognize EGFR exon 20 as a distinct driver mutation?

Zofia Piotrowska, MD: The guidelines have been updated to recognize this as a unique driver. The take-home is that an EGFR exon 20 insertion is a unique driver in lung cancer, and it can't be considered in the same category as EGFR exon 19 deletions and L858R mutations.

Transcript edited for clarity.