EGFR-Mutant Lung Cancer: Initial Approach

Transcript:Benjamin P. Levy, MD: I think it’s important that we identify EGFR mutations upfront for our patients with advanced lung adenocarcinoma. If they’re positive, we want to offer a tyrosine kinase inhibitor with either afatinib, gefitinib, or erlotinib. What we’ve seen from these agents is that they improve response rates, progression-free survival, and, most importantly, quality of life—more so than chemotherapy. Anytime I’m talking to a patient, I always integrate a quality of life discussion in the context of the therapy I’m giving them.

These 3 drugs all have superiority over chemotherapy, but they have some toxicities. It’s important that the data suggest that they improve quality of life more than chemotherapy, but there are associated toxicities that we also need to consider when we’re trying to improve quality of life. The most common toxicities that we see with these tyrosine kinase inhibitors are rash and diarrhea. Some of this can be profound, and we really have to be aggressive in the management.

I’d say, all in all, most of my patients with EGFR-mutant lung cancer see a dramatic improvement in quality of life when I start that tyrosine kinase inhibitor. Even if they do have a rash and diarrhea, they seem to have less symptom burden, less shortness of breath, less cough, and less pain when they get a tyrosine kinase inhibitor. It speaks volumes for the importance of identifying these patients upfront. You have to do the testing. You can’t give the drug unless you identify the mutation. Rest assured, if you identify the mutation, you can improve their quality of life—even if they have some toxicity with the drug—by delivering a TKI. I think the message here is that these drugs work. They’re better in terms of tolerability, and they’re better than chemotherapy in terms of quality of life. But, you can’t get it unless you have the mutation.

Luis E. Raez, MD: If a patient already has an EGFR mutation, we have already multiple studies that show that the best choice is a tyrosine kinase inhibitor instead of chemotherapy. So, we don’t use chemotherapy anymore. Among the options, we have 3 FDA-approved tyrosine kinase inhibitors in America, and there is 1 more approved overseas. Based on this, you have to choose what the best agent is.

Most doctors consider these 3 agents to be similar, and the big difference is in toxicity. Based on that, or based on your own experience, we make a choice of which one to use. It would be misleading to say that one is better than the rest or one is inferior to the rest. For example, the oldest one, gefitinib, uses a dose that is far from the maximal toxic dose. So, that is the one that is easy to tolerate. There is less diarrhea and less rash. There is another one called afatinib that has been very successful, even rescued patients that have failed other tyrosine kinase inhibitors. This is stronger, and that’s why, based on the patient, you decide to be aggressive or you decide to be more conservative. That’s the way that we choose among those 3 agents in America.

For some, erlotinib is the most popular in America because it was approved before, when gefitinib and afatinib were not available. Nowadays, I don’t know how the market share is, but erlotinib is probably the most popular in the United States.

Benjamin P. Levy, MD: When we identify an EGFR mutation for a patient with lung cancer, the goals of therapy, unfortunately, are still palliative. I want to start with that. Patients who are savvy—who have found out that they have a genetic alteration in which we can give a targeted therapy—say, “Well, you’re going to cure me with that targeted therapy.” We’re not, but we can certainly extend survival to unprecedented time frames if we look at the survival of patients now, compared with 5 or 10 years ago.

What I tell patients is that we can improve their quality of life. We can extend their life. We can probably improve their symptom burden, but we can’t cure them. It’s important to have that balanced message. The goal is palliative, but the goal is to extend life, to make life better, and to palliate symptoms. I think that’s achievable with the tyrosine kinase inhibitors that we have right now. I think it’s important that we remain optimistic but realistic with these drugs, and balance that message. With the patient who’s EGFR-positive, I tend to be more on the optimistic side than I am with other patients who don’t have any targetable genetic alterations.

Transcript Edited for Clarity