Several Breast Cancer Studies to Be Presented in Berlin May Change Practice

[Hopeful]

Chris Twelves, MD, is Co-Scientific Chair (ECCO) of the ECCO 15 and 34th ESMO Multidisciplinary Congress. Dr. Twelves is also a Professor of Clinical Cancer Pharmacology & Oncology at the Cancer Research UK Clinical Centre in Leeds.
OncologySTAT: Dr. Twelves, we understand that results from several important phase III studies will be presented at the upcoming joint meeting of the 15th Congress of the European CanCer Organisation (ECCO) and the 34th Congress of the European Society for Medical Oncology (ESMO). Would you share some information about these presentations with our audience?

Dr. Twelves: Yes, happy to do so. As we had hoped, a number of late-breaking clinical trial abstracts were submitted to the meeting. These provide up-to-date results of trials for which the analyses have just become available. Of the late-breaking abstracts, several have been selected for presentation in the breast cancer forum, and I’d like to highlight a few of those.
The first of these is a radiotherapy trial. Although obviously there is a lot of focus on new molecularly targeted agents, we should not lose sight of the fact that radiotherapy remains a very important component of breast cancer treatment, especially in women who undergo breast conservation and receive adjuvant radiotherapy as part of their local treatment. Historically, radiotherapy has been given over many weeks, often 5 or 6 weeks. This entails a lot of visits to the hospital, which is very time consuming and demanding for both patients and their caregivers.
As a result, for some years now there has been interest in determining whether an effective dose of radiotherapy can be administered in the adjuvant setting—following breast conservation in most cases—over a shorter time period. This so-called hypofractionated breast radiotherapy has also been evaluated in several different trials. For example, the START (UK Standardisation of Breast Radiotherapy) trial explored the safety and efficacy of cutting down the number of radiotherapy fractions from about 25 to about half that number, 13 or 15. This trial showed the hypofractionated regimen to be as safe and effective as the more conventional radiotherapy.
FAST trial of hypofractionated radiotherapy
Results of the FAST (Faster Radiotherapy for Breast Cancer Patients) trial, another large UK randomized trial, will be presented in Berlin. In this trial, women who had undergone breast conservation were randomized either to receive adjuvant radiotherapy administered as the conventional regimen of 50 Gy in 25 fractions or to receive their treatment essentially in 5 once-weekly fractions. This is a major difference in terms of the disruption and impact on these women’s lives.
Preliminary data from FAST, to be presented in detail in Berlin, will focus on the tolerability of this hypofractionated radiotherapy regimen.
In terms of the efficacy of hypofractionated radiotherapy in reducing or preventing local tumor relapses, the data are not yet mature. These findings may have obvious potential implications for everyday clinical practice in one of the most common tumor types.
Reducing morbidity in women with bone metastases

OncologySTAT: Besides this very interesting radiotherapy study, what other important breast cancer studies will be presented?

Dr. Twelves: Another late-breaking abstract includes results from a very different type of study, which focuses on women with bone metastases. Historically, bone metastases were a major problem for women with breast cancer 15 or 20 years ago, of course, leading to an enormous amount of morbidity. The availability of more effective therapies for metastatic disease—in particular, the introduction of the bisphosphonates—has had a major impact on reducing the morbidity of bone metastases. That progress notwithstanding, this problem has not been eliminated.
New strategies for preventing or treating bone metastases in patients with breast cancer are being investigated. An important example is denosumab, a monoclonal antibody that specifically inhibits the RANK ligand, one of the key mediators of osteoclast activity. If denosumab is effective in inhibiting the RANK ligand, the hypothesis is that this inhibition should reduce skeletal morbidity in patients with bone metastases.
Results of a large randomized trial that explore this hypothesis will be reported at the ECCO/ESMO meeting. Again, this study potentially has substantial implications for women with bone metastases, with the potential to further reduce skeletal morbidity.
Sorafenib/capecitabine combination therapy
A third late-breaking abstract, to be featured in an ECCO/ESMO presidential session, focuses on another relatively new small molecule, sorafenib, a tyrosine kinase inhibitor that has an established role in the treatment of renal and hepatocellular cancers. The study that will be reported at the Berlin meeting assessed sorafenib in combination with capecitabine, an oral fluoropyrimidine, in patients with breast cancer.
Evaluating these novel combinations is often quite challenging. The double-blind, randomized design of this phase II study enabled it to identify a signal of increased activity compared with a single- agent capecitabine, which itself has a proven track record in this disease. Overall survival data were not included in the abstract, and I don’t know whether those data will be presented in Berlin, as these were late-breaking abstracts.
Prognostic significance of axillary node micrometastases: Two studies

OncologySTAT: Besides the phase II and III breast cancer trials you’ve mentioned, can you recommend any other studies that will have an impact on clinical practice?

Dr. Twelves: Among numerous potentially interesting studies being presented in oral sessions during the congress, a study that provides a surgical-pathologic perspective is particularly noteworthy. In this study, Italian investigators explored the significance of the presence of very tiny micrometastatic deposits of cancer in patients’ axillary lymph nodes. For many years, we have been applying relatively conventional approaches to detecting axillary lymph node metastases. Analyses of large databases with long-term follow-up have clearly shown that the presence of axillary lymph node metastases is one of the most important prognostic factors in patients with breast cancer.
Now that more sophisticated tools have allowed for more systematic evaluation of lymph nodes, we have been able to identify progressively smaller tumor deposits and often isolated tumor cells or micrometastases within these axillary lymph nodes that would not have been detected previously. It has proved difficult to extrapolate from the historical data, which are based on larger metastatic deposits in lymph nodes, to determine whether these micrometastatic deposits carry the same prognostic significance.
The Italian investigators studied a very large number of patients, over 3000 consecutive patients, with up to 11 years of follow-up. While some of these patients had undergone sentinel lymph node biopsy, about a third had had conventional axillary lymph node dissection.
In another study presented in the same session, Finnish investigators also sought to determine the prognostic significance of isolated tumor cells in lymph nodes, but they limited their study to women who had undergone sentinel lymph node biopsy.
I think these 2 studies, which I believe will be presented back to back, will be of considerable interest.

Final thoughts on the 2009 ECCO/ESMO congress
OncologySTAT: Do you have any final thoughts on what oncology practitioners, especially those in the United States, should know about the upcoming ECCO/ESMO congress?

Dr. Twelves: Although as Scientific Co-Chair of the congress, I’m admittedly biased, I still think that the presidential sessions and the late-breaking abstracts are of strikingly high quality compared to what we have seen at previous ECCO meetings. We have actively encouraged investigators who had data that were not ready for presentation at the 2009 ASCO annual meeting to submit those data to this year’s ECCO/ESMO congress. For other studies that were reported at ASCO, additional analyses and updated data will be presented in Berlin. Thus, the ECCO/ESMO congress will certainly not simply be a me-too version of ASCO. In the areas of breast cancer and colorectal cancer, in particular, major studies will be reported that I think will change everyday clinical practice.

Hopeful