Selecting First-Line Treatment for EGFR-Mutated Advanced NSCLC

EP: 1.Molecular Testing Assays in Non-Small Cell Lung Cancer

EP: 2.Optimizing Molecular Testing in Patients With Non-Small Cell Lung Cancer

EP: 3.Improving Care in NSCLC: Patient Education Strategies

EP: 4.Chart Review 1: A 57-Year-Old Man With Advanced NSCLC

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EP: 5.Selecting First-Line Treatment for EGFR-Mutated Advanced NSCLC

EP: 6.Selecting Second-Line Treatment for EGFR-Mutated Advanced NSCLC

EP: 7.Chart Review 2: A 73-Year-Old Asian Woman With Advanced NSCLC

EP: 8.NSCLC: Treatment Options for Patients With Driver Mutations and PD-L1 Expression

EP: 9.Improving Outcomes in Non-Small Cell Lung Cancer: Future Directions in Care

EP: 10.Recap: Testing Options and Toxicity Management in NSCLC Harboring Oncogenic Driver Mutations

Transcript:
Gregory J. Riely, MD, PhD: For this case, the next step [is] we identify [that] the patient has an EGFR exon 20 insertion mutation....We'll talk a little bit about the data that's available. First, I would highlight that the data available for new drugs in this context is all in the second-line setting. For patients with an EGFR exon 20 insertion, for first-line treatment, we're really thinking about conventional, first-line treatment approaches. What I would highlight is that some of the more standard approaches [include what] you call platinum-doublet chemotherapy. Platinum pemetrexed would be a standard initial treatment. There also seems to be a role for checkpoint inhibitors, but it's not as well-clarified in patients with EGFR exon 20 insertions. Patients with EGFR exon 20 insertions were included in the standard trials where a checkpoint inhibitor plus chemotherapy were found to be superior to chemotherapy alone, but that was a relatively small group there. It's a little harder to tease out what the role of checkpoint inhibitors is in this context. But the specific example I’d highlight is if we found this patient has an EGFR exon 20 insertion, and let's say they also had a PD-L1 score of 60%. Lauren, how would you approach a patient with high PD-L1 and an EGFR exon 20 insertion for initial treatment for their care?

Lauren Welch, MSN, NP-C, AOCNP: Well, that would be a conversation, wouldn't it? We always go back to the EGFR paradigm that we know with osimertinib and how it does not play well with immunotherapy, wanting to be thoughtful about how we sequence therapies in that context. However, I have seen several patients with EGFR exon 20 insertions who were referred to us for clinical trials, and they had had platinum-based chemotherapy with PD-1 or PD-L1 and then went on to receive 1 of the newly approved therapies for EGFR exon 20. Anecdotally, they did fine; some of them even had some responses. I can't say definitively; I think that would be a conversation with the patient and just acknowledging [that] we're a little bit in a gray zone with these specific mutations, although my experience is that patients with EGFR exon 20 insertions have a very similar demographic. Many of them are never smokers [or] maybe Asian or Caucasian patients. Our first recommendation would probably be to hold the immunotherapy, just since we know that patients with EGFR mutations don't tend to respond as well to immunotherapy. But it would be a conversation with the patient to be sure.

Gregory J. Riely, MD, PhD: That's exactly right. Maybe the 1 thing I wouldn't do in this context—despite the high PD-L1 score—I wouldn't give [INAUDIBLE] a checkpoint inhibitor. I think that would be unlikely to be effective—particularly in a patient like the one we're talking about here who has some signs of disease, with 10 lbs. of unintentional weight loss, and things like that. Of the options, either platinum-doublet chemotherapy or platinum-doublet chemotherapy with checkpoint inhibitor would both be reasonable options.

Transcript edited for clarity.