RTP On Demand — Head & Neck/Thyroid | Research To PracticePhase II study of afatinib versus cetuximab in recurrent metastatic head and neck cancer
2:29 minutes.
TRANSCRIPTION:
DR COHEN: We know that some patients may become resistant because of mutations in the PI3 kinase pathway and, thus, the rationale for using those targeted agents. We know that some patients may have RAS mutations that may render them resistant. But we also know that there’s some patients who activate other receptors in the HER family, especially HER3. And so with that, we thought that a pan-EGFR or pan-HER inhibitor may have utility in recurrent metastatic head and neck cancer, and that’s exactly why we began to test afatinib. DR LOVE: So maybe we can go on and talk a little bit about the data that we’re aware of in terms of, first, the Phase II study. DR COHEN: This was the initial trial, a proof-of-principle study in patients with second-line, recurrent metastatic head and neck cancer, so patients who were refractory to a platinum. And we randomized patients to either afatinib at 50 mg versus cetuximab, asking the question, does afatinib have activity, and, actually, is it better than cetuximab in this setting? And interestingly, there was a crossover in the design, so patients who got one therapy were able to cross over to the other. And what we saw was, in fact, in terms of tumor shrinkage, we did see a little bit more activity with afatinib versus cetuximab, a little bit higher response rate, as judged by the investigator, for afatinib versus cetuximab, although when we looked at progression-free survival and overall survival, the 2 agents appear to be almost identical. Then, if we look at the crossover, there was something else that was quite interesting in that there were some patients — and albeit not very common — but there were some patients who did appear to benefit from the crossover on both arms. So patients who were treated with cetuximab, there were some that appeared to benefit from afatinib and vice versa. DR LOVE: So in lung cancer, there’s been some interest and even excitement about the combination of afatinib and cetuximab. What about in head and neck? DR COHEN: In head and neck cancer that hasn’t been tried. There is excitement about that combination and I do believe that there are some clinical trials that are about to do that. It just hasn’t been done yet. DR LOVE: What about adverse events? DR COHEN: Again, looking at the context of this study using the higher dose of afatinib at 50 mg, we definitely saw a high rate of the skin disorders, mostly the EGFR-related rash and a high rate of diarrhea. Many of these side effects are manageable, but at 50 mg you see a high rate. |