PracticeUpdate Oncology Best of 2018

T-VEC in Early Metastatic Melanoma Interview with Alexander van Akkooi MD, PhD by Tyeese L. Gaines DO Dr. van Akkooi is Melanoma and Soft Tissue Sarcoma Surgeon and EORTC Melanoma Group Secretary of the Department of Surgical Oncology at the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital in the Netherlands. Dr. Gaines: Could you give us a brief overview of T-VEC as a novel therapy? Dr. van Akkooi: Yeah, so T-VEC is an onco- lytic virus and it’s actually the first in class that was approved for use in melanoma patients. And what it does, basically, is first it causes lysis after you inject it into one of the melanoma metastases, and secondly it also leads to an immune response. So also, the non-injected lesions will be dealt with by the virus. Dr. Gaines: You were the senior author on a study looking at T-VEC for patients with early metastatic melanoma here at ESMO. What had prior studies demonstrated about the efficacy of T-VEC? Dr. van Akkooi: So we have the phase III OPTiM trial, which led to the registration of T-VEC, so we use that as the reference. And what we see now when we use it in real world in our institute, that we actu- ally achieve much higher response rates than with would anticipate based on that phase III OPTiM study. So wherein the OPTiM study for this indication of early metastatic melanoma you would expect about 40% responses, we’re seeing up to 80% responses. Although it is still a single institution and still a few patients and the follow-up still needs to be longer to see if the responses are also going to be durable. Dr. Gaines: When should clinicians consider integrating T-VEC into the management of their patients with melanoma? Dr. van Akkooi: I think you should consider using T-VEC for melanoma in case of the IIIB, IIIC, or IVM1a disease with cutaneous, subcutaneous, or lymph nodemetastases that are injectable. For that indication, you should always consider using T-VEC. Also consider all your other options, but that’s the group I would consider it for. www.practiceupdate.com/c/75119 CONFERENCE COVERAGE 32

Overall Survival With Palbociclib Plus Fulvestrant

Interview with Timothy J. Pluard MD by Bradley McGregor MD Dr. Pluard is Medical Director at Saint Luke’s Cancer Institute and the Paul Koontz Endowed Chair of Breast Disease at the University of Missouri–KC School of Medicine in Kansas City, Missouri. Dr. McGregor: So obviously, there’s been a lot of the technical threshold for statistical signif- icance by the study design.

presentations at ESMO this year looking at advanced treatment of breast cancer, and I think one of the ones everyone was excited about was sort of the updated analysis from the PALOMA-3 trial looking at the overall survival data. Could you remind everyone what the overall design of this trial was? Dr. Pluard : This was a trial in second-line endocrine therapy in advanced breast can- cer comparing fulvestrant with palbociclib vs fulvestrant and placebo in a phase III trial, showing a significant prolongation of progression-free survival from 4.6 months to just over 11 months. And so, this was the first look at overall survival data from that study. Dr. McGregor : What did that study show from an overall survival standpoint? Dr. Pluard: It showed a significant improve- ment in the overall survival of 6.9 months from 28 months in the placebo group to 34.9 months, which almost mirrors the progression-free survival advantage seen initially. It was not technically statistically significant, and as we talk about in many trials that are statistically significant, but we always question the clinical relevance. I think this is the converse of that. This is clearly clinically significant to show an overall survival advantage for CDK4/6 inhi- bition, despite the fact that it didn’t reach

Dr. McGregor: I think I have a sense from our discussion so far, but how does this data either reinforce or change the way you treat those patients who have endocrine- resistant breast cancer? Dr. Pluard: Well, I think it gives those oncol- ogists who were somewhat reluctant to use CDK4/6 inhibitors, because of the absence of an overall survival advantage, a good rationale to do so. I think one of the other concerns that we’ve had is do these patients after CDK4/6 failure progress more rapidly than they would have coming off endocrine therapy? And so, one of the additional endpoints that they presented today was the time to initiation of chemo- therapy in the two groups. And it turns out that in the group that progressed after CDK4/6 inhibitors, their time to initiation of chemotherapy was actually 9 months longer than the control group. We would expect if they progressed more rapidly that, that time would’ve been shorter. So I think that also provides some reinforcement for those concerns.

Dr. McGregor is Instructor in Medicine at Harvard Medical School in Boston, Massachusetts.

Go to www.practiceupdate.com/c/75354 to watch this interview with Dr. Pluard.

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