Melissa Johnson, MD: Ben, I fully agree with Jacob that this is a nuanced decision and it always was, right. Adjuvant therapy has always been the hardest discussion that we have with our patients. I’m also using it for patients who are stage II and III. The other part of the nuance is whether to give the chemotherapy. I’m giving my first chemotherapy-containing regimen now, and she’ll get her osimertinib to follow. But we considered not giving it as well. She had a stage III disease with N2 lymph nodes and so was at high-risk of recurrence. That’s what I’m doing.

Ben Levy, MD: Alex, your thoughts on this, and we’ll round it out with Ed.

Alex Spira, MD, PhD, FACP: I have little to add a couple of things. The first question is, what do you do with DFS [disease-free survival]? DFS is important, right? Preventing progression is an important thing. Especially if you look at the curves, the CNS [central nervous system] recurrence rates were down as well, and we all know that that can be devastating, even with osimertinib after. It will translate into overall survival. For those of us who’ve been around long enough, we haven’t seen curves like that in lung cancer forever that are separated, right? Call it DFS, call it PFS [progression-free survival]—those are amazing curves. For me, giving osimertinib adjuvantly for IIs and IIIs is a standard of care. For the IBs, it’s shared decision-making. When you talk to patients, most of them will probably want to do it.

I do have an issue: 3 years is arbitrary, and it’s an expensive drug. Three years is a long time. Why 3? The answer “just because you can” is not the answer you want to hear. I wish it would have been 1 year. You know it could be 5 years. I will follow this clinical trial and do 3 years. I don’t think we’re going to see studies. They discern the amount of time, although that’s an important question with a very expensive drug.

Do I give chemotherapy? I do because that’s what you’re supposed to do. In older patients, even with stage II or III, I wouldn’t. That goes into the shared decision-making. It’s how you play with the patients. If you walk in and say, “I think you should get chemotherapy, then osimertinib,” then most of them will do it. Most of us will think, “If they can’t get chemotherapy due to age or something else, they won’t.”

Ben Levy, MD: Nice summary, Alex. Ed, your thoughts to round us out?

Edward Kim, MD, MBA: Yes, there are 2 things. One is that it’s going to be this discussion of risk-benefit of the chemotherapy and whether to give it by itself without. That’s a discussion—as several of you pointed out—you’ll have with patients, and there’s no right answer.

The aspect I want to focus on—I agree with what everyone has said—is that we need to shift our mentality. All of us have been in thoracic medical oncology for quite some time. There’s been no hope. Remember the bevacizumab days when it was, “Hallelujah, we finally have something.” This is a different era. This completely transformed how we need to perceive and how patients need to perceive themselves. This is now a breast cancer early-stage mentality. These folks take a lot of adjuvant therapy, and they take pills for years to prevent disease from coming back or to add benefit. We need to shift and look from that side of the spectrum and make sure our patients understand that we’re getting there. We have adjuvant chemotherapy that helps. We have additional therapies. If you must take this pill for the next several years because it’s going to benefit you, absolutely. We’re still waiting for some of those data, but this is the next step toward that model.

Ben Levy, MD: I agree. Go ahead, Jacob.

Jacob Sands, MD: I want to ask you a question. I like that you raised the topic of bevacizumab because that’s something where initially we had a lot of enthusiasm and progression-free survival. But the overall survival wasn’t so impressive. What happens with the overall survival data that aren’t impressive? The question that’s wrapped into that is, Ben, do you think there are people who are cured from this? Is this going to ultimately lead to patients who are cured, who even when they’re off the osimertinib will still continue to be disease-free?

Ben Levy, MD: It’s hard for me to believe that this robust of a DFS won’t translate into an OS [overall survival]. That’s No. 1. No. 2 are the preliminary data we have to show that there’s a CNS protective effect, looking at people in this trial who recurred in the brain. Early on, [there was] only 1 patient in the osimertinib arm but 10 in the placebo arm. Maybe that’s what’s going to drive the OS here: the CNS protective effect that we’re seeing. Back to Alex’s point about 3 years. Is 3 years enough? Should patients be on it longer? I’m betting that this will show an OS if only because we have a CNS protective effect very early on. We’ll see, I could be wrong. It wouldn’t be the first time I was wrong. But we’re going to potentially get there.

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