Zoledronic acid disappointment for early breast cancer

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Published: 19 Jan 2011
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Prof Michael Gnant - Medical University of Vienna, Austria
Professor Michael Gnant talks to ecancertv at the 2010 San Antonio Breast Cancer Symposium. Zometa, an osteoporosis drug from Novartis, failed to improve disease free survival of early breast cancer patients in a substantial clinical trial. The AZURE trial included 3360 patients from 174 centres. Prof Robert Coleman, of the University of Sheffield, England, and colleagues including Prof Gnant, randomized stage II and III patients to standard therapy or standard therapy plus zoledronic acid for five years. The use of Zometa made no difference to survival in the study's overall population though there was some benefit in older patients. There was a 29 percent improvement in overall survival observed in the 1,101 patients who were five years post-menopause. Prof Gnant also discusses his abstract on the carry-over effect of adjuvant zoledronic acid: “Comparison of 48- and 62-month analyses of ABCSG-12 suggests that the benefits of combining zoledronic acid with adjuvant endocrine therapy persist long after completion of therapy”.

2010 San Antonio Breast Cancer Symposium, 8-12th December, USA


Interview with Professor Michael Gnant (Medical University of Vienna, Austria)


Zoledronic acid disappointment for early breast cancer

The press conference was about the presentation of the AZURE results, long awaited, a huge adjuvant trial of adjuvant zoledronic acid added to standard adjuvant treatment and nicely complimenting the patient selection we had studied previously in the ABCSG-12 trial. The results were surprising and, in fact, thought provoking I would call them. Overall it’s a negative trial, there is not too much difference in terms of the primary endpoint which is disease free survival, but it’s very interesting to see that in that large trial they see in a significant subgroup of patients, which is those women with breast cancer who are clearly after menopause, more than five years after menopause, they see a significant disease free survival benefit but also a significant overall survival benefit – 30%, which is huge.


They were not able to demonstrate such a benefit in the pre-menopausal setting which obviously raises the question what’s the difference between the ACSG-12 pre-menopausal patients and the AZURE pre-menopausal patients and the clinical difference is that ovarian function suppression was not used in AZURE. And that’s the thought provoking thing in terms of the science behind it – obviously you need double action to quiet the bone marrow microenvironment, bone markers but also oestrogen suppression which is really very interesting.


So what’s next?


It’s going to be a difficult situation in terms of the clinical application because on the one hand at first sight we have a negative trial which is usually not very good for approval of drugs and regulatory and business perspectives. On the other hand we now have at least two subgroups of breast cancer patients, post-menopausal patients and pre-menopausal patients on ovarian function suppression, and together they comprise three out of four patients in the whole breast cancer population. So I’m pretty sure that many physicians around the world will consider adjuvant treatment with zoledronic acid in these situations in the future.


What else were you presenting at SABCS 2010?


The updated ABCSG-12 results show another scientifically interesting aspect and that is the persistence of the benefit long after the completion of therapy. To remind you, in ABCSG-12 it’s three years of intervention and then all treatments stop and patients go without any further treatment. Now we have results beyond five years, in some patients even out to beyond ten years, and we see a complete persistence, clear persistence, of that reduction in disease relapses and improvement in overall survival. This is not what we usually see in oncology or in medicine, usually we have to treat and when we stop treatment the benefit goes away. Obviously when we target the bone marrow microenvironment, and I find that exciting as well as reassuring to patients, it might be good enough to do an early time limited intervention and patients will still derive long term benefit and maybe even increase the cure rate which is just great.