Treating Beyond Progression in EGFR-Mutant Lung Cancer

Transcript:Luis E. Raez, MD: Usually, we start treatment with any of the tyrosine kinase inhibitors, but at around 9 to 12 months, patients start to develop resistance to these agents. The patients have new resistant mutations, and they start to clinically fail treatment, so we need to change treatment. Usually, by 9 to 12 months of treatment, 50% of the patients start to fail.

Benjamin P. Levy, MD: The decision to switch therapy on a patient who is EGFR-mutated and developing progression is complicated. Progression for a patient who’s EGFR-mutated is heterogeneous. Some progression is small; the tumor may be growing ever so slightly, and the patient is asymptomatic. For those patients, I may try to continue the tyrosine kinase inhibitor. If the patient is doing well—they have a small amount of growth on their scan, yet they are doing all right otherwise—that’s a time to consider continuing with the TKI.

For a patient who has developed oligometastatic disease—where the overall burden of disease is stable, but one new spot is growing—I think we have reasonable data to address that spot with either stereotactic radiosurgery, surgery, or local ablative therapies and continuing with the TKI.

I think the decision to switch to a new drug is dependent on a few things. The first is the pace of cancer growth. The second is the presence of symptoms the patient has. And then, most importantly, the third is the presence of a T790M mutation. All those things should be factored in. But, there has to be a lot of critical thinking at progression. When I talk to my fellows, I say, “The upfront decision is very easy. For a patient who’s EGFR-mutated and stage 4, choose your TKI—either erlotinib, afatinib, or gefitinib. Then, when progression occurs, that’s where a lot of hard decisions have to be made that aren’t so clear-cut and require some critical thinking.”

Luis E. Raez, MD: The patients have a very good quality of life nowadays with targeted therapy like TKI inhibitors. So, the patient maybe develops 1 single metastasis in the liver or in the renal gland. There’s now the opportunity to do stereotactic radiation therapy to control that area, so the patient may benefit from a tyrosine kinase inhibitor for more time; we don’t need to change therapy. We call that oligometastatic disease. Of course, if the patient needs one of these tyrosine kinase inhibitors, and they develop 10 new metastases, it’s scarier because you don’t want to delay their change in treatment. So, that’s why this concept of oligometastatic disease is more or less new in oncology, and we try to keep the patients in the same treatment as long as the patients are developing minimal progression—meaning 1, maybe 2 lesions, and the lesions are easily controlled with stereotactic radiation.

Transcript Edited for Clarity