ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago
Interview with Professor Michael Gnant (Medical University of Vienna, Austria)
The influence of zoledronic acid on the treatment of endocrine-responsive early breast cancer
What did you present at ASCO 2010?
What we are going to present this time at ASCO is material results of the ABCSG-12 Trial. That's a trial on 1,800 premenopausal women with endocrine responsive breast cancer. They were treated without adjuvant chemotherapy, but based on the endocrine responsiveness of the tumour, with ovarian function suppression, plus Tamoxifen or Anastrozole. Most important, there were two more groups in this trial, where zoledronic acid, the bisphosphonate, was added at a dose of four milligrams twice a year, for a total treatment duration of three years.
We presented the first results two years ago, and this time there is an update based on 40% more events, and just some maturity in the data, so enabling us to give information on different subgroups about the main effect.
The main result is that when you add the bisphosphonate in the adjuvant setting, in this particular patient group, that you will improve disease free survival by more than 30%, meaning that the addition of zoledronic acid twice yearly will help in keeping this metastasis away, both in bone, but also outside bone, but also improve the local regional result, which is very exciting. And these data have now matured. This is very stable. We see that even on over-survival there is about a 35% reduction, which is just not quite statistically significant, but a clear-cut trend. And most importantly, what we see is that this effect can be utilised, irrespective of the underlying endocrine treatment, so it’s more or less similarly present, both in the Anastrozole group, in the Tamoxifen group, it’s present in patients with node-negative breast cancer, as well as node-positive breast cancer. So this is actually exciting, because it further adds to the story of an actual anti-cancer potential of bisphosphonates.
How do bisphosphonates achieve this effect?
There are several putative mechanisms of action. Bisphosphonates have long been known as exerting some direct as well as indirect anti-cancer effects. Personally I believe that most of the effect we observe in the adjuvant setting will be an indirect effect on the microenvironment, so we are not really directly attacking tumour cells, which are not present in the adjuvant setting anyway, but we are changing the microenvironment to a less fertile soil, according to the seed and soil hypothesis. And this means that obviously it’s more difficult for dormant micro metastasis to break up at some, even late point after the initial diagnosis and treatment. So I believe that most of the effects in the adjuvant setting will work through those indirect effects on the bone marrow.
What message should patients take from the results of this trial?
We now have several pieces of this puzzle coming together. There is additional data at this conference about similar effects in myeloma patients. We have seen very recently a publication on the effect of zoledronic acid on micro metastasis. So I believe we now have, from a variety of different angles, reasonable evidence that zoledronic acid can be used as an anti-cancer drug in addition to protecting bone and protecting the skeleton, which is obviously a very important message.
These data are currently being scrutinised by the regulatory authorities, both in the US and elsewhere in the world, and hopefully this treatment will be available to many patients in different countries later this year.