You’ve been looking here in this study at older patients with breast cancer, what were you trying to do?
We tried to find out how far a more moderate type of chemotherapy is effective in improving the outcome of elderly patients with moderate to high risk early breast cancer. We randomised for that 1,350 patients, so that’s the largest trial in elderly breast cancer patients so far, to receive either ibandronate alone, a bisphosphonate, or ibandronate in combination with six cycles of capecitabine.
So it was a reasonable idea to treat them just with a bisphosphonate?
Yes. There were three reasons, actually, for doing that. First simply pragmatic, that we wanted to avoid an observation control arm without treatment because that makes always compliance problems. The second is that we know, of course, that elderly women have a high risk for bone related events, fractures and osteoporosis and these things, and that can be protected by giving a bisphosphonate. Also we know from now, confirmed by large meta-analyses, that the use of bisphosphonates improves breast cancer survival. So it’s a good backbone, actually, a non-toxic backbone for these patients.
So you had quite a big study, you added or did not add capecitabine, what happened?
Unfortunately we could not demonstrate that capecitabine significantly improved disease free survival. We were seeing at five years an absolute difference of 3.8% and the curves seemed to separate but probably as 80% of these patients had hormone receptor positive disease in these trials usually you see treatment effects only very late and we had a median follow-up time of five years now. So maybe that was a little bit too short but that’s, of course, a hypothesis but it strongly supports to follow-up these patients for longer to see how far there is maybe a late effect for capecitabine. But currently there is not.
Were there any subgroups that benefitted or might have benefitted on capecitabine?
The group where you can observe differences, usually earlier, are those with hormone receptor negative tumours, as I said 20%. So not too many, 220 patients in the study. The hazard ratio was going into this direction but the p-value also was there not significant.
So you were looking for a gentler therapy in these women, median age 71 years, what are your conclusions from these findings?
Together with a previously reported study, the CLGB study, comparing capecitabine with AC or CMF chemotherapy which showed that especially in hormone receptor negative tumours the combination chemotherapy was better. I would say that the more aggressive the tumour is mono-chemotherapy is not an option. Then we have to try to somehow make a poly-chemotherapy feasible and tolerable to these patients whereas maybe in other more favourable situations it might be not a good thing to give capecitabine but rather than no chemo to avoid unnecessary side effects.
Indeed, in the study that you’ve just reported it was reasonable to not give chemotherapy, just the bisphosphonate. So does this suggest that there’s scope for advising or discussing with patients not having chemotherapy perhaps more than has been considered?
The disease free survival was 75-78% at five years so there is a substantial relapse rate. So these patients are really at risk, this is number one. So they are patients that really require chemotherapy. Second, the overall survival at five years, so at this time these patients had a median age of 76 years, it was 90%. So these patients, they have a long life expectancy so they will experience all the risk of breast cancer quite comparable to younger age groups. So with that the decision to give chemo or not to give chemo should be according to the biology. We have all these gene tests around or we have other ways on assessing this, but it should not be concentrating on age actually.
So not an automatic decision and needs to be individualised. What are your recommendations then, finally, to sum this up for doctors?
I believe we have now a lot more experience on giving, for example, weekly paclitaxel also in elderly patients in combination with then an anthracycline in sequence. So this is my practice, I try to convince the patient let’s start, let’s find out, we can modify the dose if necessary. But every cycle that you get is actually beneficial for you in the situation where chemotherapy is indicated.
So the very brief ten second take home message about whether to use capecitabine and what to consider using, what is that brief message?
In elderly patients requiring chemotherapy, mono-chemotherapy with capecitabine is not an option. Poly-chemotherapy has to be preferred.