RTP On Demand — Head & Neck/Thyroid | Research To PracticeCase: A patient who experienced a response to pembrolizumab for locally recurrent disease
4:29 minutes.
TRANSCRIPTION:
DR COHEN: We had a patient who we treated on the clinical trial with pembrolizumab who presented with recurrent, locally recurrent neck disease. And this was a patient who was symptomatic from their neck disease. In fact, it was even starting to break through the skin, so fairly severe disease. He was refractory to, already, 2 lines of therapy. So he’d had a platinum. He’d had a taxane. And really at that point, there aren’t very many treatment options. And fortunately we had opened this study with pembrolizumab, and he was eligible and enrolled. DR LOVE: I guess we should point out that’s the anti-PD-1 agent that was just approved in melanoma. DR COHEN: That correct. And so we started treating him. And what was interesting is at the first assessment, when he came back, his neck disease was actually larger. And we began to get concerned, because first, was he not responding and was he progressing on this agent. But secondly, as you can imagine, the disease now begins to get close to some critical structures like vessels. And so we decided, knowing what we knew about immunotherapy mostly in melanoma, we decided we would watch him very closely, monitor his disease, monitor his symptoms but try to keep him on therapy. And lo and behold, by 8 weeks, the tumor began to shrink. And then by 16 and further on down the road, it began to shrink even more. He’s still on therapy. It’s now been about 8 months, and he’s had a very nice partial response. DR LOVE: And was he having any side effects? DR COHEN: Very minimal, almost really no side effects. DR LOVE: Maybe you can comment a little bit about the biology of immune therapy and where anti-PD-1 fits in. DR COHEN: Yes. So really, discoveries made probably about a decade ago, maybe a little bit more, knowing that, first of all, there’s a duality in regulation of the immune system. So there are receptors and ligands that turn on the immune system, mostly T cells. But at the same time, there have to be receptors and ligands that can turn them off, or inhibit T cells. Otherwise, every time we responded to a virus, we would die. We have to turn off the immune system. So realizing that that was inherent in the normal function of the immune system, we began to look at that in the context of cancer. And what we found was that cancer usurped these systems. So cancers are able to, first of all, downregulate the stimulatory receptors and upregulate the inhibitory receptors. And one of the major ones that cancers upregulate is this PD-1/PD-L1. Knowing that, companies and investigators began to develop antibodies or blockers to these inhibitory systems, and some of the first that came into the clinic were actually CTLA-4, which have been approved in melanoma, and then eventually PD-1. And what’s amazing about the PD-1 inhibitors or PD-L1 inhibitors is they appear to work in a variety of solid tumors and specifically in the context of our discussion, there’s activity in recurrent metastatic head and neck cancer. DR LOVE: There’s been discussion, mainly in other tumors, about predictors of response, particularly PD-L1 ligand. Was this man tested? DR COHEN: He was tested. The – for the clinical trial, there had to be expression at – at some level of PD-L1. What’s interesting — and this is mostly from the lung data — is it does appear that expression of PD-1, and especially PD-L1, can be predictive of response. And the higher the expression, the more likely the response. We’re still sorting that out in head and neck cancer. That is probably going to be true, but the exact cutoff we don’t know for sure, because there are clearly patients who express this at low levels who can respond. But then the converse is also true. There are patients who express high levels who don’t respond. So it’s not as simple as one marker, as often it is in cancer therapy. |