RTP On Demand — Head & Neck/Thyroid | Research To PracticeLUX-Head & Neck 1: A Phase III trial of second-line afatinib versus methotrexate in recurrent and/or metastatic squamous cell cancer of the head and neck progressing after platinum-based therapy
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TRANSCRIPTION:
DR COHEN: So this was a study in second-line recurrent metastatic squamous cell carcinoma of the head and neck. And patients were randomized to either afatinib or methotrexate in a 2:1 randomization, with the primary endpoint being progression-free survival. Patients could have had a prior EGFR inhibitor, that is, prior cetuximab. That was allowed. The patients were stratified for that. And then the data were positive for the primary endpoint. So progression-free survival was actually improved versus methotrexate with a hazard ratio of about 0.8. Statistically significant. But when we look at the numbers, the difference was only about a month in median progression-free survival. So not incredibly impressive. And there was no difference in overall survival. So in terms of how clinically meaningful this is, that becomes a bit of a challenge. Now, the difference in progression-free survival is also supported by an improvement in patient-reported outcomes such as pain and swallowing, global health as well, all in favor of afatinib. And an improved response rate and disease control rate. Again, all in favor of afatinib, suggesting that there is some utility to the difference in progression-free survival but it’s not as dramatic as we would have hoped. I think afatinib is an effective agent in second-line recurrent metastatic disease. It’s a bit more effective than methotrexate. It’s not dramatically more effective. And the challenge now is, are there patient groups that may benefit more? And that’s beginning to come out. We presented a follow-up abstract at ASCO suggesting that patients with EGFR amplification and with an intact PI3-kinase pathway that’s not mutated, that’s not altered, that is a relatively inactive PI3-kinase pathway, seemed to fare better with afatinib versus methotrexate. And, of course, we’re exploring that much more. DR LOVE: And that ties into what you were saying before. I was surprised, too, in your ASCO data set, I saw that you looked at VeriStrat®, which I’ve only heard about in lung cancer. DR COHEN: Right. There are some data in head and neck cancer looking at. Essentially, what we saw in the afatinib study is that, just as we know from lung cancer, VeriStrat is prognostic. Interestingly, even though afatinib, of course, is an EGFR inhibitor, it didn’t appear to be predictive for afatinib, but it was certainly prognostic. Patients with the good profile on VeriStrat did significantly better than those on the poor in both arms. |