New insights in Merkel cell biology and treatment

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Published: 18 May 2017
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Dr Paul Nghiem - University of Washington, Seattle, USA

Dr Nghiem speaks with ecancer at EADO 2017 about recent updates in treatment options for Merkel cell carcinoma.

He considers response rates to immunotherapy and ongoing biomarker surveillance as guidance for combination therapy.

Dr Nghiem spoke with ecancer at AACR 2016 about using pembrolizumab as treatment, and data on avelumab for metastatic MCC was presented at AACR 2017 by Dr Howard Kaufman.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

It’s been an exciting year for Merkel cell carcinoma. Until very recently when this cancer became advanced the way to treat it was with cytotoxic chemotherapy and although that would shrink it in about two-thirds of cases most patients would have their disease progress by 90 days after starting chemotherapy and then they would be very refractory to subsequent therapies of almost any kind. So the advent of immune therapy has been exciting to the field and we now have data from three trials that are public suggesting that indeed PD-1 pathway blockade is very effective in this cancer. The pembrolizumab data was published in The New England Journal and led to the first listing for Merkel cell carcinoma in the National Comprehensive Cancer Network guidelines in the US. So patients can now get this agent. Then the avelumab trial has now led to the first FDA approval for an agent for Merkel cell carcinoma in March so that’s a big deal to patients.

Even more recently, just a few weeks ago, the nivolumab data came out, so all three agents effectively blocking the PD-1 pathway and all showing pretty consistent and excellent responses, significantly higher in the setting of patients getting their therapy naïve, without prior chemotherapy.

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For sure. About half of patients really benefit from immune oncology therapies, single checkpoint agents in other words, the PD-1 blockade. However, the other half we’re struck with several problems. One is to predict who that’s going to be and number two is, of course, to help them respond. We’ve already seen some responses in combination in isolated cases to patients who were refractory to checkpoint inhibition but obviously the real goals would be to predict who is going to need which kinds of therapies beforehand and give them the right therapy in advance. For better or for worse that’s going to take quite some time to get to that stage.

It’s going to take a village to attack this problem and markers in the blood, markers in the tumour in particular; circulating factors and things will be very helpful in figuring out who needs what kinds of combinations. The concept that you would do an early on trial biopsy is also very appealing. We’ve seen responses - when this cancer responds we see it often in days and the response is very dramatic and rapid. So by doing a biopsy one or two or three weeks in that could be very informative as well.