Adjuvant Osimertinib as a Standard Therapy for EGFR-Positive NSCLC

Treatment with osimertinib (Tagrisso) after surgery significantly reduced the risk of death in adults with completely resected EGFR-positive stage IB, II, or IIIA non-small cell lung cancer (NSCLC), according to updated data from the ADAURA trial presented at the American Society of Clinical Oncology (ASCO) annual meeting.

MedPage Today brought together three expert leaders in the field: Moderator Roy Herbst, MD, PhD, of Yale Cancer Center in New Haven, Connecticut, is joined by Julie Brahmer, MD, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, and Sarah Goldberg, MD, MPH, also of Yale Cancer Center, for a virtual roundtable discussion. This third of four exclusive episodes focuses on the overall survival analysis from ADAURA.

Following is a transcript of their remarks:

Herbst: Topic number three. Some fellow [Herbst himself], I don’t know him that well, presented this ADAURA study at ASCO [on] overall survival [OS]. So how important is having overall survival now in the ADAURA study? And maybe say a few words about it, Julie.

Brahmer: Well, sure. With the ADAURA data, I already had drank the Kool-Aid with the improved disease-free survival. I really do feel that patients do benefit from the osimertinib in this setting. And I think with the overall survival being about 85% compared to 73% at 5 years and having a hazard ratio of less than 0.5, that’s amazing. And it just adds a cherry on top.

And I think it gives us even more data to be able to tell our patients — particularly those patients who are worried about toxicities and concerned about going on an oral therapy that they have to take every day — that this truly does make a difference in survival, in addition to keeping the cancer away. I don’t think we can discount having overall survival data. Obviously, I would love to have even longer-term overall survival data, but this is very helpful.

Now, I think based on some of the data, my patients are even less likely to want to come off at 3 years and they’re wondering, should I just stay on the therapy even longer?

Herbst: Absolutely. Now, Sarah, what’s your experience when you talk to patients and even before this, but now with the OS data, how do you fit this into your armamentarium?

Goldberg: I also have been using adjuvant osimertinib for awhile, since we had the disease-free survival data. That was just such impressive disease-free survival results. Before that, I used to think we needed OS to change practice in the adjuvant setting, but the benefit of disease-free survival, and also brain mets [metastases] recurrence, was so striking that I’ve been using it in my patients since then.

But as Julie said, I think it just adds additional rationale, additional reason, that we should be doing this. Obviously, improving overall survival is the gold standard in the early stage, and if it does that, it should be considered in all patients with EGFR mutations.

I think the one piece that I maybe am a little more pushy now on than I even was before is the stage IBs. I think we’re just so used to not treating those patients — the 3- to 4-cm tumors, node-negative. I think now that we have overall survival data and it seems to benefit even the stage IBs, I’m using it in my — I just actually right after ASCO just had this experience with a patient with a less than 4-cm tumor, I think it was 3.5 cm or so, and recommended it.

So I think it’s absolutely the standard of care and just speaks to the importance, as we mentioned before, of getting EGFR testing on the biopsy sample. So we don’t want to just know it from the surgical sample after they already had neoadjuvant therapy. We want a diagnosis before the decision is made of what neoadjuvant therapy they’re getting. I think it really is critical to get that.

Herbst: In that patient you talked about, did you recommend chemotherapy too? Do you still need the chemotherapy?

Goldberg: Yeah, so I think actually you answered this at ASCO — it was a good question someone asked you — which is the study didn’t really address whether chemotherapy is necessary. It wasn’t a [chemotherapy] versus osimertinib study. Patients were allowed to have chemotherapy, although many of them didn’t. Or some of them didn’t, I should say.

I don’t think this tells us we can’t use or we shouldn’t use chemotherapy. I think the decision about chemotherapy and the decision about osimertinib are completely separate, right? You still have to take into account the same things we’ve been taking into account for years about the benefit in the various stages and the performance status and toxicity and all of those factors. I think for a lot of people for stage IBs, the 3- to 4-cm tumors, I tend to not use [chemotherapy] in those patients anyway. So in my patients, we didn’t give chemotherapy, but I did give her adjuvant osimertinib.

But otherwise, for stage IIs and IIIs, there still is a benefit — as far as we know, and it’s not different now — there still is a benefit with adjuvant chemotherapy. So I still think [with] chemotherapy, same decision making as before and now just the addition of adjuvant osimertinib.

Herbst: Okay. Julie, your thoughts on chemotherapy in a stage II or a III? You still give it?

Brahmer: I still give it. I’m worried about tumor heterogeneity, that not all the tumor may have that as a driver mutation. And we know that some of the mutations tend not to do as well just on single-agent osimertinib in the metastatic setting. So my thought is give chemotherapy — we know that it does benefit patients — and then give the osimertinib after.

So I have a group of patients who we’ve done exactly that, and thus far I have not regretted it. And actually the chemotherapy was not hard to tolerate. It’s really getting them through the osimertinib for 3 years has been more of the issue. But I think with everything that we’re doing now and working hand in hand with our pharmacists and other support staff to keep these patients on therapy is very important.

Herbst: Great. And last question, either of you. Worldwide, is it going to be an effect now of the survival data, you think it’ll convene? There are some countries that haven’t approved it or reimbursed it. Think that may have an impact, Sarah?

Goldberg: I sure hope so. We know that EGFR mutations are really common in parts of the world, especially Asia. I would hope that all of those patients are able to access adjuvant osimertinib. There’s survival benefit. There’s not that many things that we have in oncology where there’s a survival benefit that improves cures. So I would hope so, but I guess I’m not enough of an expert on world politics to know how that will work. I would sure hope so.

Herbst: I’ll give you my thought. You know, I think certainly the disease-free survival itself at 80+%, with preventing metastases of the brain, it was quite convincing. But now with the survival, I think it’s quite good. Some have criticized the crossover in the trial, and you remember this trial was started before osimertinib was even approved in the frontline setting in the U.S., and not to mention most of the countries. About 90% of patients got an EGFR TKI [tyrosine kinase inhibitor] and relapse. About 45% or 50% got osimertinib. And now everyone who’s progressing well.

So we’ll have to see the results as time goes on. And the nice thing is the trial is continuing to be followed; ctDNA [circulating tumor DNA] is available and that’s being collected and will continue to be collected. So more data to come from ADAURA.

Click here to watch the other videos from this ASCO roundtable series on immunotherapy.

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