Factors to Consider in Treating EGFR-Mutant NSCLC

Roy S. Herbst, MD, PhD:The goals for this patient’s therapy are to treat the symptoms, to treat the disease burden, and then to keep the patient alive for as long as possible. Many patients withEGFRmutations can live for many, many years, because they get the first agent—hopefully they don’t become resistant to it for quite some time—and then they get the next agent. Now, of course, we have newer agents such as osimertinib in this area that target the most common form of resistance called theT790Mmutation. So, this is a very hopeful situation.

Multimodality therapy is critical, because if we find a patient who has disease in the brain, for example, or of the CNS, one might want to treat that. In some cases, we might just use the EGFR agent alone first, but if someone has significant brain lesions, we might want to use gamma-knife, or radiosurgery, as some call it—whole-brain radiation. So, that’s important to know. We also want to know if there are any lesions any place else in the body that are of high risk to the patient and might need radiation therapy early on—certainly, surgery as needed. But it is important to do a multimodality evaluation and look at the patient from stem to stern to understand what the burden of disease is and what local therapy might be needed.

All of cancer therapy is a balance between local and systemic therapy, and one needs both. I don’t think you’re going to cure someone with systemic disease with just local therapy, but you certainly can treat some symptoms, which will allow the patient to remain on the systemic therapy for longer periods of time and have a greater chance of benefit.

The performance status is the most critical feature I look at in this or any patient. And a performance status of 2—I haven’t met the patient, but I’m told it’s 2. It could be my 2 or my colleague’s 2. Some people’s 2s are better 2s than others, and you really do need to see the patient. I have enough experience now, after many years, that I can tell who can get chemotherapy and who can’t. When I hear 2, immediately the light bulb in my mind goes off: We probably can’t use chemotherapy, or if we did use chemotherapy, maybe we should use a single agent. Then again, it will be a palliative therapy at best with chemotherapy. Then, when I hear it’s a performance status of 2 and it’s a patient who has anEGFRmutation, I get excited for the patient and try to communicate to the patient that there is a therapy that can hopefully shrink the tumor. You might notice a benefit within a couple of days, almost immediately, so why not try it?

Sometimes, you have to convince the patient to do it, because these patients can be quite sick and wheelchair-bound. But this would be the patient where I would say, “Look, your performance status is diminished, you’ve got widespread disease—let’s give this drug a try for a couple of weeks and see what happens.” The good thing is that the testing is usually quick: in most centers, less than 2 weeks, usually sooner. The drugs are usually available. Most places are quite familiar with the major side effects of an EGFR inhibitor—rash and loose stool—and we move forward.

So, for this patient, it might be a perfect therapy. They probably need some pain medication for the bone metastases. The oral EGFR agent will probably act to help with any constipation that might provide. And then, we hope to see response, and we follow these patients. Bone metastases are a difficult disease to treat, but hopefully the metastases, the lung lesion, and the other disease in the body will be treated. The good news here is that this patient does not have brain disease yet. He might, at some point, get that; we have to keep an eye out for it. But right now, we are full speed ahead to start the EGFR therapy and then, of course, manage the patient carefully, because we do know that resistance will develop. It’s not if, but it’s just when.

When you think of the modalities of care for lung cancer, supportive care has to be right at the top of the list—especially since, in most cases, we’re still treating palliatively, although our goals are more ambitious than they were. Here, we’re using an EGFR inhibitor, and hopefully this patient will have a nice response and feel better. But early palliative care and supportive care have been shown to improve outcomes in patients with lung cancer and need to be used as early as possible. We are treating the entire patient, so, if this patient were in my clinic, I would probably begin palliative care measures with oral pain medicines, but I would also refer them to a palliative care service to help as well.

For a patient like this, who I’m starting on an EGFR inhibitor, I’d probably want to see him at least monthly, but normally I work very closely with a nurse practitioner. I would have either her or me see the patient in 2 weeks. I like to do this for a number of reasons, as interstitial lung disease develops with these agents, you hardly ever see it, but I’ve seen it a few times; it happens in 1 in 500 patients, or maybe a little bit less. I just like to bring someone in and see how they’re doing. It also gives us a chance, as long as they don’t live too far away, to check their skin and to check how they’re doing with diarrhea and other side effects. In this case, we could monitor the pain. So, I usually like to see the patients early on and then on a monthly basis, and I would do scans every 8 weeks.

Transcript edited for clarity.

• 65-year-old male, former smoker (25 pack-years, quit 12 years ago) presented complaining of persistent lower back pain, extreme fatigue, shortness of breath, and a 25-lb weight loss in the past 6 months.
• PMH includes rheumatoid arthritis which significantly limits his physical activity.
• Back pain also limited the patient’s daily activity.
• MRI of the spine showed evidence of multiple lesions, but none were causing cord compression.
• CT of the chest showed a 4-cm mass in the left lung, with enlarged bilateral mediastinal lymph nodes.
• The MRI of the brain revealed no metastases.
• ECOG PS was assessed to be 2.
• He underwent an endobronchial ultrasound-directed biopsy of the mediastinal lymph nodes.
• Pathology revealed poorly differentiated adenocarcinoma.
• Molecular testing showed a mutation in EGFR exon19 deletion.