Review of AENEAS Trial and Similar Agents

Experts in cancer care review the phase 3 AENEAS trial with aumolertinib and the cost-effectiveness.

Mark Socinski, MD: I’ll ask Jack and Gilberto to weigh in on 1 of the more interesting abstracts. This year was the phase 3 trial looking at—I think I’m pronouncing it right—aumolertinib. When I looked at the data, I thought I was looking at the FLORA trial. It’s almost superimposable on the date. Does anyone want to take a crack at reviewing the study design, or can I ask Jack to do this and give your thoughts about that?

Jack West, MD: Sure. The AENEAS trial is aumolertinib vs gefitinib [Iressa] in a Chinese patient population with EGFR mutation–positive previously untreated disease. It’s a 1:1 randomized study of 429 patients to either a treatment of aumolertinib at the dosage of 110 mg daily vs a treatment of gefitinib at 250 mg daily. This is a youngish population, so almost all patients are 60 years old and just under two-thirds of the patients in both arms were women. More than two-thirds are never-smokers, and almost all the population hasn’t had any carcinomas.

The highlight is that there was a difference in progression-free survival [PFS] that echoed what we saw with the FLORA trial and blew our minds in fall 2017. That was when we saw the data without overall survival. What we see is a median PFS of 19.3 months with aumolertinib vs 9.9 months with gefitinib, and a hazard ratio of 0.46, which is extremely significant. The response rate wasn’t very different, which is what we also saw with FLORA, and about every patient subgroup—brain metastases, age, mutation, performance status—all highly favored aumolertinib.

The safety of aumolertinib looks very good and really doesn’t have any signals of toxicity issues. If anything, it may have lower diarrhea rates than we would expect to see from some other drugs. In fact, there was about a 16% rate of any grade diarrhea with aumolertinib vs more than twice that—about 36% with gefitinib, but gefitinib is generally not that toxic. If we were talking about afatinib [Gilotrif] or erlotinib [Tarceva], the differences would be quite pronounced.

Overall, I wouldn’t want to overstate it. It’s a cross-trial comparison when we make inferences about osimertinib [Tagrisso] vs aumolertinib, but the results look astonishingly similar. It’s another agent that has a phenomenal difference in progression-free survival against a worthy competitor that we had previously thought was a great choice until 2017. It’s not against chemotherapy, it’s against another EGFR inhibitor, and we don’t have CNS [central nervous system] activity, so that has become, as I already alluded to, an aspect of something we want so that we have a choice. When you have osimertinib with CNS activity better than some alternatives, we don’t want to give that up.

We also like the tolerability of osimertinib in general—it’s not perfect, but it’s pretty darn good. Aumolertinib looks to be in that ballpark. I don’t know if we can split hairs about which medication is better, but you don’t seem to be giving up anything, in terms of tolerability, with aumolertinib. We don’t have overall survival, though I’d be optimistic that it’s going to echo what we’ve seen with osimertinib, but we don’t know that. There are some data still to be obtained, but compared with what we saw in 2017 on FLORA, this looks remarkably like that. If you had obtained that data, you could replicate it with a drug that costs less than half of what osimertinib does. To me, that’s overcoming 1 of the biggest barriers. The only thing that would make us hesitant about osimertinib is its high cost.

Mark Socinski, MD: Gilberto, you alluded to some of your Asian colleagues, not necessarily seeing the data in Asian populations as similar to Caucasian populations. Is there any concern, from your perspective, that there’s a population issue with this Chinese experience? Or are EGFR mutations a biologic of that?

Gilberto Lopes, MD: That’s a great point. Before we knew the EGFR mutation story and learned about alt translocations and other rare yet significant driver mutations, we had the big question, “Is the trial, done in Japan, something we can extrapolate and use to infer what’s going to happen in California or Florida?” With EGFR mutations, with the known specific subtype and the ability to stratify for all the factors that interfere, we don’t know about TP53, and we don’t know a few other things that bear some importance in prognosis and predictability of treatment. But in general, we would think that these things can definitely be extrapolated.

I wouldn’t be worried that this is a trial that was done specifically in Asia. It wouldn’t be different from if this was a trial in gastric cancer, as Afsaneh Barzi can talk about later. But for patients with EGFR mutations, we would believe that these data are most likely true, and we should be able to extrapolate them to the United States, the West, Europe, and Latin America.

Transcript Edited for Clarity

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