EGFR Exon 20 Insertion As A Therapeutic Target in Non-small Cell Lung Cancer - Episode 6

Treatment Selection for Patients With EGFR Exon 20 Insertions in NSCLC

Zofia Piotrowska, MD, shares insights on factors to consider when selecting the appropriate therapy for patients with EGFR exon 20-positive NSCLC.

Matthew Fowler: What is the first-line treatment option for patients with EGFR exon 20 insertion-positive non–small cell lung cancer?

Zofia Piotrowska, MD: Although we now have 2 approved targeted therapies for these patients, unfortunately, neither of them is approved in the frontline setting. There are some ongoing clinical trials looking at first-line treatment options for these patients. But as of today in 2021, the preferred first-line treatment for these patients is still platinum-based chemotherapy, carboplatin and pemetrexed. The role of immunotherapy for these patients is still an open question about whether we should be giving them first-line chemotherapy and immunotherapy combinations, or whether perhaps patients with EGFR exon 20 insertions may have less benefit from immunotherapy. We’ve seen that in the case of more common sensitizing mutations, where immunotherapy alone is certainly less active than in other types of lung cancer. It’s still an open question whether these patients should receive chemotherapy alone or chemoimmunotherapy, and it’s something that needs to be decided on a patient-by-patient level and in discussion with patients. Both mobocertinib and amivantamab are approved options for second- or later-line therapy, so when your patients progress on that platinum-based chemotherapy regimen, that’s when we start thinking about these new approvals.

Matthew Fowler: With these 2 agents we’ve been discussing that have received recent approvals, what are some of the treatment options for patients who might progress on these?

Zofia Piotrowska, MD: Before we talk about what treatment options might be available for patients who have progressed on amivantamab and mobocertinib, many people have asked me, how should we be selecting between these options? How do we think about mobocertinib and amivantamab, again, both approved for second- or later-line therapy? It will be a discussion with patients as to some of the safety profile differences in these drugs, some of the logistics and how they’re administered, and picking what’s best for patients. Amivantamab is an IV [intravenous] therapy. It’s administered initially weekly for the first 4 weeks of treatment, and then every 2 weeks thereafter. So it requires patients to come to the clinic on a regular basis. Whereas mobocertinib is an oral therapy, and so often, patients will prefer an oral therapy. Although with mobocertinib, we see that patients can have frequent and sometimes high-grade diarrhea. Both of these are important considerations, so we have to talk to patients and decide which of these factors makes one of these drugs the preferred second-line option for each individual patient?

We’re now seeing new drugs in development beyond mobocertinib and amivantamab. We’ve seen recent data presented at ASCO [American Society of Clinical Oncology annual meeting] last year from a drug from Dizal [Pharmaceuticals], DZD9008; another drug from Cullinan Oncology, CLN-081; and a number of others in development. In the future, both of these agents are effective, but there is still lots of room for improvement in terms of both efficacy and safety. CNS [central nervous system] penetration will be an important issue going forward. Many of these patients have brain metastases, and we’re still learning about the CNS activity of these compounds. But we are worried that maybe they’re not as CNS active as we’d like, so going forward, we will need new and better treatments, but it’s certainly exciting to have these options available to us today.

Matthew Fowler: Is there a role for sequencing mobocertinib and amivantamab?

Zofia Piotrowska, MD: That’s a very important question, and the short answer is that we don’t know yet. There is probably a role for sequencing these 2 agents because when we think about patients with stage IV lung cancer, we want to think about using all of the options at our disposal to help keep their cancer in check. But we don’t know what the optimal sequence is, whether perhaps amivantamab would be effective after mobocertinib, or the converse, whether mobocertinib would be effective after amivantamab. That’s something we’re going to have to learn going forward, and that will be an important question in terms of how we decide how to sequence these agents in the future.

Transcript edited for clarity.