Selecting First-Line Treatment for EGFR-Mutated Advanced NSCLC


Experts briefly reflect on optimal frontline treatment strategies for a patient who presents with EGFR-mutated advanced non–small cell lung cancer.

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.

Related Videos
Expert on NSCLC
Experts on NSCLC
Expert on NSCLC
Expert on NSCLC
Experts on NSCLC
Expert on NSCLC
In terms of tumor control, treatment with cabozantinib and atezolizumab led to an overall response rate of 19% among patients with advanced non–small cell lung cancer, according to Joel W. Neal, MD, PhD.
Experts on lung cancer
Expert on lung cancer
Related Content