PracticeUpdate Oncology February 2019

CONFERENCE COVERAGE 24

EflapegrastimforReducing SevereNeutropenia Interview with

Baseline Circulating ESR1 Mutation Analysis From the EFECT study Interview with William John Gradishar MD, FACP by Farzanna S. Haffizulla MD, FACP, FAMWA

Lee S. Schwartzberg MD, FACP by Farzanna S. Haffizulla MD, FACP, FAMWA

Dr. Haffizulla : You’re the lead author on a study looking at eflapegrastim compared to pegfilgrastim for the pre- vention of neutropenia among breast cancer patients. Can you tell us a little bit about the design of the study and any key findings? Dr. Schwartzberg: Eflapegrastim is a new drug that is a long- acting growth factor. The business end of the molecule is GCSF, so a typical granulocyte-colony stimulating factor molecule, but it’s linked in a different way than pegfilgrastim or biosimilars. So it has an FC component on it, and that FC component, the antibody actually increases its residence in the bone marrow, and also increases the receptor occupancy in the bone marrow on granulocyte progenitors. So it has a little different biology, and it also has a long residence time, so it’s a long-acting growth factor. The study was designed to show non-inferiority between pegfilgrastim and eflapegrastim in breast cancer patients who were receiving TC chemotherapy. The study design was using 3.6 mg of the new drug versus 6 mg standard dose of pegfilgrastim, so it’s a more potent molecule. What the study showed was non-inferiority in terms of the dura- tion of severe neutropenia in the first cycle and across all four cycles of TC chemotherapy. So this is a study that hopefully will support the registration of this drug and we hope to see it on the market in the near future. It’s actu- ally the second study that was done with almost identical findings and design, so we now have two studies of sev- eral hundred patients comparing in TC chemotherapy, eflapegrastim to pegfilgrastim, and seeing the same thing. Dr. Haffizulla: That is the prior data that essentially showed… Dr. Schwartzberg: Right. We published that at ASCO and presented at the MASCC meeting this summer on the first study. Dr. Haffizulla: Do you envision this particular drug being commonly integrated into practice in the future? Dr. Schwartzberg : I do. I think this is going to be an alternative to the long-acting growth factors that are out there now. And of course it will depend on its cost, its efficacy, toxicity, all of those things, but so far, the efficacy is wonderful. Toxicity is very similar to pegfilgrastim, so we’ll see how the market shapes up in the future. Go to www.practiceupdate.com/c/77341 to watch this interview with Dr. Schwartzberg.

Dr. Gradishar is Betsy Bramsen Professor of Breast Oncology, Division of Hematology and Medical Oncology in the Department of Medicine at Feinberg School of Medicine, Northwestern University in Chicago, Illinois.

Dr. Haffizulla: You’re one of the authors on an interesting study looking at the prognostic effects of circulating ESR1 mutations on outcomes among patients in the EFECT study. Can you tell us about the EFECT study a little bit more? Dr. Gradishar: Sure. So, the EFECT trial was something you have to go back in history, actually more than a decade ago, and it was a study that we were doing to try and sequence optimally anti-hormone therapy. Cutting to the chase, it was a population of patients with metastatic dis- ease post-aromatase inhibitor and then they would either get fulvestrant or exemestane. So, that trial was sort of a wash in terms of saying one agent was better than the other, and it lay fallow for the next decade and a half, but fortunately, they had samples that were still available from that trial. And today, in the era where we’re looking at markers trying to predict who’s going to benefit, who’s going to have resistance to a par- ticular therapy, those became a valuable resource. So, we were able to go back and look at the samples, blood samples, looking for muta- tions in the estrogen receptor, so ESR, whether it was present or not. And a significant fraction of all the patients who were in that original trial so long ago had samples preserved all this time. And what was deter- mined was that you found a high frequency of ESR mutations, perhaps not surprising because all of these patients had gotten an aromatase inhibitor. But in those patients who had an ESR mutation present their " …it tells us that when you’re exposed to aromatase inhibitors the probability of having

an estrogen receptor mutation is higher and it really speaks to the notion of doing precision medicine as a guide to therapies that we may have now and in the future. "

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