Immune tolerance and the microenvironment in head and neck cancer
Prof Gilberto de Castro - Instituto do Cancer do Estado de Sao Paulo, Sao Paulo, Brazil
According to the TCGA data, usually head and neck squamous cell carcinoma presents with a very large mutation burden and it is related to a high immunogenicity. But, on the other side, there are too many signals in the microenvironment of these cancers that cause an immune tolerance to these cancer cells. For example, a decreased expression and secretion of interferon gamma; we have a decreased expression of surface molecules related to T-cell activation like CD137 and OX40 and an increased expression of some molecules related to energy of these T-cells, like PDL1 and PD1.
We had a presentation in the last ASCO annual meeting held in Chicago this year where Dr Seiwert presented the data of the KEYNOTE-012 trial and in fact it was presented an expansion cohort of more than 130 patients. They were all treated with pembrolizumab, 200mg every three weeks. Pembrolizumab is an antibody directed to PD1 and in this trial they detected a response rate of 25% and 56% of these patients presented some kind of decrease in measurable lesions. Most interestingly, in those patients with responding tumours the duration of response was not yet reached. In general, this treatment was well tolerated and I would like to stress that globally there are other trials, clinical trials, investigating these agents and one of them is the trial called KEYNOTE-048 in which those patients with recurrent or metastatic head and neck squamous cell carcinoma, they were not amenable to be treated with radiation or surgery and they will be randomised into three arms. The first arm pembrolizumab alone; the second arm pembrolizumab plus chemotherapy, platin and fluorouracil, and the third arm the reference regimen called EXTREME – cetuximab plus platin fluorouracil. I think that we need to collaborate with these trials in order to better characterise what are those patients who can most benefit of these drugs. Because, for example, we don’t know yet the correct dose, correct regimen, the toxicity profile and we need to develop some biomarkers related to response in order to develop, for example, some cost-effectiveness data.