Treatment Approaches After Adjuvant Osimertinib

Neal Navani, MRCP, MSc, PhD: Let’s talk about the issue of the duration of treatment. Gary, I can come to you briefly. Let’s say you’ve given a patient 3 years of osimertinib. What then?

Gary Doherty, MRCP, PhD: Given that it’s not reimbursed in the United Kingdom, that’s a very “What if?” question. With checkpoint inhibitors, that patients are understandably reluctant to come off treatment at 2 years. I’m on the edge of my seat with adjuvant osimertinib. It’s terrifying, right? It’s an arbitrary time point, and we don’t know—we presume we’re suppressing micrometastatic disease. We need to see these data before we decide exactly how to follow up with these patients. Do we have to stop at all? Well, yes. That’s what the data say.

I wouldn’t be surprised if we had a significant number of relapses within that first year. The question is thus: Is osimertinib curing these patients? Or is it suppressing micrometastatic disease that will eventually grow wider? Then the question is, what do we do with patients who have relapses at various points during treatment? It’s an important question. What about patients with early relapses after starting adjuvant osimertinib? They have intrinsic resistance, so their experience will be different from patients who develop metastatic disease or relapse when they’re having adjuvant osimertinib. Then there are those who’ve relapsed after finishing the full 3 years—or whenever they stopped because of toxicities—of adjuvant osimertinib. Those are completely different scenarios—we’re not entirely sure what to do. Presumably, in the latter scenario, whenever we stop osimertinib—they have proven themselves to be sensitive—as long as it’s the same disease, they’re likely to respond to a rechallenge of osimertinib within the metastatic space. The other cases are going to be a lot more challenging to deal with, I’m afraid.

Neal Navani, MRCP, MSc, PhD: Do you have any idea what follow-up strategy you’re going to be employing for these patients? Is it going to be a CT scan every 3 months, 6 months, or annually?

Gary Doherty, MRCP, PhD: Whenever they’re on a given treatment, we can relax. Whenever our patients stop adjuvant treatment, we need to pursue a very swift initial follow-up, I would advocate. There are no clear guidelines on this, but I’d be particularly worried about the first couple of months after stopping adjuvant osimertinib—then we can go and then settle down into a 3-month regimen, but these things are far from concrete. We’ll learn as we go along and as we get more data from longer-term follow-ups with the ADAURA trial. It’s a very difficult clinical decision.

Neal Navani, MRCP, MSc, PhD: Thanks, Gary. Christian, what’s your experience been like with patients who’ve completed 3 years of osimertinib treatment? What do you do then? What’s your discussion with the patient like? What do you do?

Christian Grohé, MD: At the moment, we’re still following these patients in our cohort, who’ve contributed to the ADAURA study. Obviously, the pattern of metastases in these patients’ cases has differed. That’s coming back to the idea that, obviously, local metastases play a more important role in the cases of patients who have long-term treatment early on. To be honest, we don’t have a real strategy in terms of the standard of care. We’d like to see if this is the cohort of patients where, based on their resistance patterns, and in the tissue specimens we’ve obtained, we have treatment options for these patients, including systemic combinations of chemotherapy plus certain treatment options.

This is definitely a matter of learning on the job at the moment. I believe these suppress the clonal expansion of the EGFR-mutated lung cancer, as long as we treat these patients. If some patients have an early relapse—that’s what I was saying at the beginning of the discussion—we do a lot of liquid biopsies. We have interesting results. It’s very important for us to be monitoring disease burden and escape mechanisms in this cohort of patients with driver mutations. I hope we can contribute, with this liquid biopsy data from that study, to understand how to treat these patients who come up to or are getting close to 3 years of the osimertinib, as in the ADAURA trial.

Neal Navani, MRCP, MSc, PhD: Thank you. Solange, if I could come to you for the same question briefly—off protocol. You’ve come to 3 years of osimertinib treatment. What do you do then?

Solange Peters, MD, PhD: Based on the data, it looks like there’s a proportionally increased risk of local relapse for these patients. I’d still apply what I do for all comers as patients. There’s no guideline for the follow-up of patients. The idea is that you follow a patient to be able to introduce a subsequent treatment, which would be beneficial in case you find a relapse. There might be an isolated lesion and progression, or there might be—because addressing chemotherapy, chemotherapy-I/O [immuno-oncology], or another strategy is beneficial earlier compared with later in treatment. What I would do is apply the usual thing. It depends on each country, but we would follow the patients with a CT scan every 3 to 4 months for 2 years, then semesterly at every 6 months for 1 or 2 additional years. We usually stop at 5 years. Based on what we’ve established as being something that looks routinely feasible, I’d still apply that to these patients. But remember, we don’t have these guidelines for all comers. It’s quite improbable that we have very good signals to help us there in the EGFR. Maybe we can perform the liquid biopsy. Maybe we’ll see what the tick of relapse in patients is, molecularly defining relapse and then looking at radiological exams in the future. We need a little more time.

Transcript Edited for Clarity