35th ESMO Congress, 8–12 October 2010, Milan
Interview with Professor Jan Vermorken (Antwerp University Hospital, Edegem, Belgium)
The Spectrum Study
Thank you for giving us a couple of minutes on ecancer medical tonight. You’re a very busy guy, you’re the new editor of Annals of Oncology, congratulations, but you’re also giving some really important talks here at ESMO and particularly the head and neck one stands out. Would you like to tell us, for people who are not at the ESMO meeting in Milan, what it’s all about?
During this symposium we are going to report for the first time the data of the Spectrum Study.
And what was that?
Spectrum is a large phase III trial that has been performed in patients with recurrent metastatic squamous cell carcinoma of the head and neck.
Well the four main sites, so it’s oral cavity, hypopharynx, oral pharynx and larynx and these are all recurrent disease. It’s first line setting, so it means the patients can have had chemotherapy in the primary disease setting for curative intent – chemoradiation, or they could have had induction chemotherapy followed by radiotherapy.
And so these patients were randomised to receive the standard Wayne State University protocol that is Cisplatin 100 per m2 followed by four days of 5-Fluorouracil with a dose of 1000 per m2 per day and that is the control arm. In the experimental arm this was combined with Panitumumab which is a fully human monoclonal antibody against epidermal growth factor receptor.
Which receptor does it hit?
The HER1. And that drug was given at a dose of 9mg/kg every three weeks and the plan was to give these treatments for a maximum of six cycles and then the patients could have the possibility in the experimental arm to continue with monotherapy Panitumumab.
The antibody only?
Yes, the antibody only for as long as they benefitted from it or whether they had an acceptable toxicity. This was, of course, only in the patients that were responding or had stable disease at that time.
Now the assumption was, the protocol was organised such that we needed about 650 patients and 470 death events in order to come up with an expectation of a difference of about three months in median survival from 8.7 to 11.7 months. Now to make a long story short we didn’t reach that. We found a difference of 2.1 months so there is a difference.
So that’s something.
That’s something but it is supported that there is an effect by a significant difference in progression free survival and a significant difference also in response rate and disease control. So there is no doubt in my mind that this again is showing activity in this disease and this would confirm, to some extent, the Extreme study that has been published two years ago.
Yes, it is a pity for all of us that we didn’t have the primary endpoint reached but that doesn’t change the idea that it is an active compound.
And most of these antibodies do work better with chemotherapy, that’s what we’ve seen from other experiments.
Yes, also pre-clinical work suggests that it’s really synergistic with chemotherapy.
What’s your gut feeling about the role of maintenance Panitumumab? Any grip on that?
There has never been a protocol where the concurrent use of oral Cituximab or Panitumumab with chemotherapy was compared with the same plus maintenance, so we cannot give an answer to that. So we really don’t know it.
You have a feeling for that?
Well if governments would be really interested this would be something that you should do in a country because it will perhaps reduce costs if you knew that the efficacy would be the same without maintenance. So it’s worth doing a study like that.
What’s the next study that you guys are doing in Belgium and in your international market?
Of course this was, for the first time in about thirty years, that we ever saw a benefit, anything in recurrent metastatic disease. So we hoped that this was the start of something beautiful so we now have several trials that show a beneficial effect of these monoclonals with chemotherapy. The next step is to combine other biological agents in combination with this. So, for instance, we have started to do a study with MERC where Cilengitide which is a compound that has antiangiogenesis aspects, to combine this with what we found in the Extreme study. The study has been closed for entry now so we wait until further results but that’s an interesting step again. And, as you know, Cilengitide seems to have some interest also for the treatment of brain tumours, so we wait, it’s one of the possibilities.
Jan, thank you very much indeed. We really appreciate meeting up with you again.