Benjamin P. Levy, MD: We’ve talked a lot about the role of TKIs in the advanced stage setting. These drugs are falling into the natural progression that most drugs follow in oncology; they start in later stages and then move to an earlier stage. I’m not talking about phases, but stages of disease. We are learning more and more about the curative potential of EGFR TKIs and resected EGFR-mutant lung cancer. There are ongoing trials. Jonathan, what do we know so far about adjuvant TKIs?

Jonathan W. Riess, MD, MS: There have been several trials in EGFR-mutant lung cancer, going back over the past several years, looking at adjuvant EGFR TKI therapy for earlier-stage non—small cell lung cancer. None of them, as of yet, have shown a clear overall survival benefit. One, several years ago, even showed a potential toward harm in an unselected population. With these newer-generation drugs, and with the first- and second-generation EGFR TKIs, in the EGFR-mutant non—small cell lung cancer population, we’ve really wanted to know if we can get the benefit that we see in the metastatic setting if we bring that forward into the earlier setting.

A study that was presented at last year’s ASCO Annual Meeting, that recently published, looked at gefitinib versus cisplatin/vinorelbine in stage 2 and 3A non—small cell lung cancer. It was mainly conducted in China. It was an open-label phase III study, and it randomized patients to receive either cisplatin/vinorelbine or the first-generation EGFR TKI, gefitinib. It did show a disease-free survival benefit: 28.7 months median disease-free survival versus 18 months. That was intriguing and promising. We’re studying it here in the United States in the ALCHEMIST trial. As part of that NCI-sponsored trial, patients with EGFR exon 19 or L858R mutations are randomized to observation after standard-of-care treatment.

Stage 2 and 3 patients will receive adjuvant cisplatin-based chemotherapy, followed by either erlotinib or observation. This is going to be a critical study to see if there really is a survival benefit. In a lot of these other studies, once you stop an EGFR drug at 2 years or so, the curves look great for disease-free survival and then start coming down once the drug is stopped. Are you really improving survival or are you just moving the goal posts a little bit, suppressing things until you take them off? This is something that needs to be determined.

Now that osimertinib is approved for the metastatic setting, bringing that into the adjuvant setting, at an earlier stage, would be critical. If that shows the same benefit as it did in the metastatic setting, and is better than first- and second-generation options in the earlier stage, it could be really promising for patients in the future.

Benjamin P. Levy, MD: This is a call for clinical trial enrollment. We need these answers. I think there is an adjuvant osimertinib trial going on right now. We, of course, have the ALCHEMIST trial, which we continue to try to put patients on. Is anyone comfortable using adjuvant TKI therapy off of a clinical trial? Is there ever a scenario where the patient’s enthusiasm overflows and drives the clinical decision making? Does anyone ever have an issue with that, where a patient wants that targeted therapy because they’ve been told that they have a target? “How can you not give me a targeted therapy?”

Jonathan W. Riess, MD, MS: That’s a great question. I do not, and I adamantly do not because we don’t yet have trial data to support that as standard of care. That’s why we’re doing these clinical trials. As mentioned, although it was more of an unselected population, a study that came out several years ago showed that there was a potential toward harm. I offer the clinical trial, and I’m very adamant about not doing it off label.

Zofia Piotrowska, MD: For the highly motivated patients, they can be referred for a trial. Outside of a clinical trial, these drugs can have serious side effects. I think we need more data before I would feel comfortable prescribing them.

Transcript Edited for Clarity