ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago

Interview with Professor Robert Coleman (Weston Park Hospital, Sheffield, UK)

Costs and benefits of bone metastases therapies

You’re dealing with patients for whom quality of life is extremely important, so just simply preventing some symptoms may not be the only thing, or it may indeed.  What exactly are you doing for patients at this point in their life?

Well, I think patients with advanced cancer affecting bone can have a pretty miserable time.  They get a lot of pain.  They often can’t continue with their work.  They can’t function socially.  They’re on large doses of analgesics often.  So, if you can prevent some of that unpleasant morbidity, then, you know, it really does transform quality of life.  There have been many studies showing that bisphosphonates improve quality of life.  Interestingly, in the denosumab-zoledronic acid studies, there were quality of life assessments, and there, just reducing skeletal complications a little bit further improved quality of life a little bit more.  There’s some very nice quality-of-life data in the breast cancer study from Lesley Fallowfield’s group showing that.

How much of a hint of improved overall survival do you think we’re getting at the moment?

I think in advanced cancer, we’ve only really seen survival benefits in those patients with the most aggressive bone disease.  So, if you pick a population who have got very high rates of bone turnover, then it is possible for a bisphosphonate to improve survival.  Now, we don’t quite know why.  In that situation it probably is not a direct anti-cancer activity.  What it is probably doing is keeping the patient fit enough and able enough to come and have their underlying cancer treatment, because we don’t give chemotherapy to patients sitting on an orthopaedic ward having to have their hip pinned or with hypercalcaemia.  So, in a way, it’s maintaining performance status and encouraging the oncologist to continue an active treatment approach.  We’ve seen that in lung cancer, where time is precious, if you don’t get your treatment in quickly, then patients will do badly, and to a certain extent, in advanced prostate cancer.

If I could refer back to the head-to-head comparison of zoledronic acid with clodronate that Gareth Morgan and his colleagues, the MRC study, have conducted.  There was quite a big survival advantage.  What are your comments about that study and that sort of approach?

I think the MRC-9 study was a very ambitious trial, because it was trying to answer several questions at once about types of chemotherapy, about the role of thalidomide as a maintenance therapy, and then this third question about, which is the best bisphosphonate to use?  So, when you’re asking many questions, you’ve got to make sure that one comparison doesn’t influence the results of another.  So, at the moment, you know, we’ve seen – if you like – the headline results for this clodronate versus zoledronic acid comparison.  It looks very impressive.  I would like to know whether the benefit is greater with one particular type of chemotherapy or a particular subset of myeloma patients, or whether it’s generalisable across all patients.  But, I think the thing that makes me feel that it’s a very important result is that it’s not just an improvement in overall survival but it was being driven by an improvement in complete remission rates, which is the most important thing to achieve in myeloma.  If you get people into complete remission or very good partial remission that will translate to overall survival, and that we’re seeing.  I think the myeloma experts feel that that is evidence that there was some kind of direct anti-cancer activity with zoledronic acid, not just protecting against bones.

What could be the scope of denosumab in the setting of multiple myeloma?

At the moment, we don’t really know because there are only a few myeloma patients included in one of the randomised trials – just over 100 patients – and that was too few to make any firm conclusions.  In that small number, it didn’t look better than zoledronic acid, unlike in every other cancer where it’s been tested.  So, I think for that reason plus the fact that we’ve seen the survival advantage in zoledronic acid, people are going to be particularly keen to use denosumab at the moment.  I believe there’s a further denosumab versus bisphosphonate trial just starting or in progress.  We’ll have to wait for the results, but myeloma is, I think, one disease where denosumab probably doesn’t have a role at the moment.

Talking about bone disease in myeloma but also breast cancer and prostate cancer as we have, what’s the bottom-line message that you would like to leave busy cancer doctors with?

I think the key message to cancer doctors is don’t forget the bones.  They’re very important for quality of life.  I think all patients should be considered for bone-targeted treatment and then, which one you use depends on individual circumstances, health economics, etc.  But the most important thing is to give some kind of bone-targeted treatment to these patients, and at the moment, many patients are missing out because, particularly, our younger oncology colleagues don’t remember how bad it was before bisphosphonates.