RTP On Demand — Head & Neck/Thyroid | Research To PracticeEGFR inhibition in head and neck cancer
3:18 minutes.
TRANSCRIPTION:
DR LOVE: Let’s talk about targeted therapy. Maybe you could just comment a little bit on the issue of EGFR in head and neck cancer, biologically. DR COHEN: Here’s an example where we’ve known that EGFR is expressed at very high levels in squamous cell carcinoma of the head and neck, especially HPV-negative disease. And in fact, it’s among the highest tumors in terms of expression of EGFR. So we’ve known that the target is there. We’ve known that EGFR expression is prognostic. What we haven’t been able to effectively do is take patients who express this target and demonstrate a survival benefit in that group. And here’s a table that shows some of the experience, both Phase II and Phase III, that EGFR inhibition does have a response rate, but it’s modest as a single agent in an unselected patient population. It’s somewhere in the range of about 10%. And unfortunately, most Phase III trials have not been positive in this setting using an EGFR inhibitor. With afatinib now, as I said, presented at ESMO, being the exception, a positive Phase III study in recurrent metastatic disease. DR LOVE: And, of course, we’ve heard about afatinib in lung cancer. We’ve also heard about this agent, dacomitinib. What do we know about that in head and neck? DR COHEN: This was an interesting trial for a couple of reasons. First of all, dacomitinib is also a pan-HER inhibitor, so all 4 receptors in the EGFR family. And what this trial was able to demonstrate is that this is a drug that’s also active. And what the investigators did was they did some genomic and pathway analysis to try and figure out which patients actually were the ones to respond. And it turns out that —about a 12% response rate. And it turns out that patients who have mutations in the PI3 kinase pathway are actually less likely to respond than their wild-type counterparts. And so we’re beginning to develop biomarkers that may be able to select patients who are most appropriate for EGFR inhibitor therapy. DR LOVE: And I guess EGFR mutations, some mutations don’t occur. DR COHEN: They don’t. We know that, of course, in lung cancer there’s a group of patients who have tyrosine kinase mutations and appear to benefit tremendously from these drugs. Those mutations simply do not occur in head and neck cancer. DR LOVE: So we see, obviously, panitumumab is another EGFR antibody that’s used in colon cancer. What about it in head and neck? DR COHEN: So a Phase III trial was, in fact, conducted in head and neck cancer, first-line, recurrent, metastatic, very similar to the EXTREME study, adding panitumumab to, now, this time only cisplatin/5-FU versus cisplatin/5-FU alone. And what’s interesting is that this was statistically a negative study. A couple of things to note: First of all, numerically there was a difference, so panitumumab improved median overall survival by about 2 months. But the control arm did much better than the control arm on EXTREME. So the control arm here had a 9-month median survival. And the study was simply underpowered to show a difference, given the 11-month that we saw with panitumumab. So panitumumab is actually not approved for the treatment of recurrent metastatic head and neck cancer. |