PracticeUpdate Oncology Best of 2018

CONFERENCE COVERAGE 31

European Society For Medical Oncology 2018 Congress 19–23 OCTOBER 2018 • MUNICH, GERMANY Pembrolizumab for Recurrent HNSCC

© ESMO 2018 Congress

those two biomarker-enriched populations, pembrolizumab was better than extreme chemotherapy. Dr. Gaines: Should these results change the way that clinicians are treating recurrent head and neck cancer? Dr. Burtness: I think that, for the biomarker- enriched patient population, it looks like pembrolizumab monotherapy leads to better survival than the extreme. There was a second randomization in this, or there was another experimental arm in this trial, which was the pembrolizumab chemotherapy group, and there, the only mature data we have are for the overall patient population. But there again, the combination of pembrolizumab with chemotherapy seems superior to the extreme regimen for an unselected patient population. So, I think that we have two potential new standards. One is pembrolizumab monotherapy for patients who have PD-L1 expression on their tumors, and the other is the novel combina- tion of pembrolizumab with chemotherapy for all-comers. Given that pembrolizumab plus chemotherapy includes the side effects of chemotherapy, it seems likely that we’ll be deciding between pembrolizumab monotherapy and pembrolizumab plus chemotherapy based primarily on people’s PD-L1 expression, but alsomaybe on the bur- den of their cancer, how symptomatic they are, because the chemotherapy-plus-pem- brolizumab arm did have a slightly higher response rate.

Interview with Barbara Ann Burtness MD by Tyeese L. Gaines DO Dr. Burtness is Professor of Medicine (Medical Oncology) and Disease Aligned Research Team Leader at the Head and Neck Cancers Program, and Co-Director of Developmental Therapeutics Research Program at Yale Cancer Center in New Haven, Connecticut.

Dr. Gaines: You’re presenting the results of KEYNOTE-048 today, at ESMO this year. What group of patients were included in this study? Dr. Burtness: KEYNOTE-048 was a trial for patients with recurrent metastatic head and neck cancer who had not previously had chemotherapy for their recurrent metastatic disease. They had to have cancer that had arisen in one of the big-four sites, so oral cavity, oropharynx, larynx, or hypopharynx, and they couldn’t be amenable to curative treatment with a local modality. So, if there was a salvage operation or re-irradiation for them, they were not eligible. Dr. Gaines: What was the dosing schedule for the different treatment arms? Dr. Burtness: Pembrolizumab was given at a flat dose of 200 mg every 3 weeks, and that was for up to 35 cycles. So that was the first arm, the pembrolizumab mono- therapy arm. Then there was a novel arm, which was pembrolizumab integrated with chemotherapy, and so, it was meant to be the same chemotherapy backbone that we used in the extreme regimen. So, it could be cisplatin or carboplatin, together with 5-FU, and again, pembrolizumab was given for every 3 weeks. That combination was given for six cycles, and then patients went on to pembrolizumab monotherapy. And then, the control arm was the standard extreme regimen.

Dr. Gaines: So, were the groups stratified by PD-L1 status? Dr. Burtness: Yeah, they were stratified by PD-L1 staining on tumor cells. We used a cut point of 50%. So, if you had 50% staining or more, you were in one group, and less, in the other. And then, they were also stratified on performance status and whether or not they had a p16-positive oropharynx cancer. Dr. Gaines: In general, what do the results say about the efficacy of pembrolizumab in this setting? Dr. Burtness: It looks like pembrolizumab is good first therapy for head and neck cancer. We did different analyses for the pem- brolizumab monotherapy arm than for the pembrolizumab-chemotherapy combination. There are going to bemoremature analyses coming for overall survival for some of the dif- ferent subsets, but looking at pembrolizumab monotherapy, we now have data on the bio- marker-enriched subsets. And I’m just going to say a word about the way the PD-L1 pos- itivity was graded here, because it’s actually different than what we used for the stratifica- tion, but we used a combined positive score. So, that was, if there was PD-L1 staining on tumor cells, lymphocytes, or macrophages, and you counted up the number of positive cells, and you divided it by the total number of cells that you had counted. So, the most enriched population was CPS- 20, and then combined positive score of 1, and so, for pembrolizumab monotherapy, in

Dr. Gaines is a Board- Certified Emergency Medicine Physician and Medical Director of Ultramed Urgent Care.

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VOL. 2 • NO. 4 • 2018