EGFR Inhibitors as Adjuvant Therapy in NSCLC

Transcript:Sai-Hong Ignatius Ou, MD, PhD: In early-stage mutant lung cancer, we would love to use an EGFR TKI [tyrosine kinase inhibitor] as adjuvant treatment. However, there is not a lot of clinical data right now to support the use of an EGFR TKI, in terms of overall survival benefit. A single-arm study showed that 5 years of adjuvant EGFR TKI therapy improved disease-free survival, but one of the major questions is, how long should we give the EGFR TKI for? My personal feeling is that once you start EGFR TKI therapy in the adjuvant setting you almost have to continue until disease progression.

Based on the recent presentation of an adjuvant trial for patients with N2 disease who were either randomized to chemotherapy or an EGFR TKI, there is disease-free survival benefit. However, the standard of care in the United States for N2 disease is chemotherapy followed by radiation. Indeed, the Intergroup trial that is being conducted in the United States for chemotherapy with or without radiation, then randomized to 2 years of EGFR TKI therapy, in this case erlotinib, had this observation.

However, I don’t think 2 years is enough. It’s arbitrary. We don’t know whether 1 year’s better, or 5 years, or an indefinite number of years. We still don’t know the data. There is an adjuvant trial that is being conducted by AstraZeneca looking at osimertinib versus observation. It is very similarly designed to the adjuvant trial. I think that trial is likely to be positive. We don’t know what the endpoint is. If the trial is positive, it’s likely that we will also use EGFR TKI therapy in the adjuvant setting. We’ll have to wait for the results of the adjuvant study, the ADAURA study by AstraZeneca, looking at using osimertinib in this setting.

One of the questions we need to answer is how to manage the adverse effects of EGFR TKI therapy. In my opinion, once you start you should not stop. Iressa, or gefitinib is tolerable, so we can potentially give it for a long period of time. Osimertinib is very well tolerated, and we could potentially give it until disease progression. However, it comes with a cost. If you need to continue to suppress the EGFR mutation, 5 years of osimertinib is very expensive, especially in countries where patients have pay out of pocket.

In the United States, insurance will cover the cost. So we have to reach a conclusion on what to do, based on the adverse effects and the cost. We don’t know yet. The adverse effect profiles are pretty well tolerated for gefitinib and osimertinib, but the duration of therapy and the cost is something that we need to consider when we look at all of the adjuvant trials.

Transcript edited for clarity.