Interview conducted by April Cashin-Garbutt, BA Hons (Cantab) on 18th July 2012
Please could you tell us a little bit about breast cancer and who it affects?
Breast cancer is the most important cancer for women in the developed world. About 20% of all patients diagnosed with breast cancer die of metastatic disease. Thus, treatment results urgently need further improvement.
Breast cancer mainly affects women. Very rarely it also affects men. Our recent research was only on breast cancer in women.
Your recent research was on bevacizumab (Avastin). Please could you tell us a little bit about this drug and for what types of breast cancer it is prescribed?
Our research was on bevacizumab, but it was included all drugs that target the vascular endothelial growth factor. However, at the moment published randomized trials are available only for bevacizumab .
Bevacizumab is an antibody directed against the vascular endothelial growth factor. In combination with chemotherapy, it is used with success in patients who have metastatic colorectal cancer. It is also successfully used in patients with renal cancer and a sub-group of patients with lung cancer.
Bevacizumab has some typical side effects which are generally well managed. These include for example hypertension. However, there are also some rare, but serious side effects which include bowel perforation and an increased risk of arterial thromboembolic complications.
At what stage of breast cancer is bevacizumab normally given?
The current review was only on metastatic breast cancer and it was only tested in combination with chemotherapy.
Please could you tell us a little bit about chemotherapy and why bevacizumab is given in addition to this therapy?
Both chemotherapy and endocrine therapy are the standard treatment options for metastatic breast cancer. A large number of different groups of chemotherapies are effective in breast cancer. It is known colorectal and lung cancer that bevacizumab is not effective without chemotherapy. The reasons for this are not clear. Furthermore, the efficacy of bevacizumab varies with the chemotherapy backbone with which it is used.
The typical side effects of chemotherapy, such as nausea,hematotoxicity and fatigue, are not associated with bevacizumab. However, bevacizumab has other toxicities, such as hypertension and an increased risk of minor bleeding. However, the risk of major bleeds is not normally increased.
How did your research on bevacizumab originate?
We thought it was a very interesting drug. We had previously written a review on the drug’s effect in colorectal cancer, so I thought it would be interesting to study its effect on other types of cancer.
Some years ago I learned about the different types of bias in the medical literature and the work that the Cochrane Collaboration does. It fascinated me for their international perspective, their sound methodology and their economic independence. I consider this work as very important so I have spent a lot of time writing Cochrane reviews. My previous one was on gastric cancer.
They are interesting because they do not just summarise the previous findings, but they extensively search for information that is missing in what has been published. This allows important discoveries to be made.
What did your recent research on bevacizumab find?
Overall the research found that bevacizumab prolongs disease progression, but not overall survival in patients with endocrine-refractory (i.e. who have previously progressed on hormone therapy or are considered as resistant to hormone therapy), metastatic breast cancer.
The difficulty is that patients with metastatic breast cancer are treated with many different lines of treatment today as there are many different treatments available. It is therefore very difficult to assess the effect of one treatment on overall survival. However, it is important to ask this question nevertheless, as the survival time and quality of life are the only reliable parameters of a patient’s benefit. Whether delaying disease progression alone is of true benefit to the patient is debatable.
What do you think were the reasons for bevacizumab adding no overall survival benefit to chemotherapy?
I don’t know! The only thing we know comes from the first trial by Katy Miller, who showed that – although there was a significantly prolonged progression-free-survival, there was no overall survival benefit, despite the fact that crossover was not allowed.
The number of patients observed until their death, however, was too small. We have absolutely no explanation for this. This is one of the major messages of the review: If you really want to assess whether there is a patient benefit of new drugs, where you don’t completely understand the mechanism of action, you need to follow the patients until their death.
Concerns have been raised over the potentially serious side effects of bevacizumab. What do you think about this and what impact do you think your research will have on the prescription of bevacizumab?
The side effect profile of the drug was known before our research, so I don’t think our work will have any impact on the prescription. There was one previous systematic review which observed a higher rate of cardiac complications for breast cancer patients treated with bevacizumab, but our work did not support this finding.
Do you have any plans for further research into this area?
This work will be continuously updated as new studies will be published. There are many open questions concerning the mechanisms of resistance and how to overcome them.
How do you see the future of breast cancer therapy progressing?
There is progress being made in many other domains of breast cancer treatment, especially in the development of more targeted drugs, for example - particularly, for HER-2positive breast cancer.
I think this is what is really needed: the identification of biomarkers and development of more targeted therapies.
One of the problems with bevacizumab is that the overall effect is modest and we do not have any idea of a sub-group of patients who really have a greater benefit than others. There has been an extensive search for biomarkers, but there have been no thoroughly convincing results. We don’t know how to identify those patients who benefit and distinguish them from those who do not.
Where can readers find more information?
The Cochrane review can be found here:http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008941.pub2/abstract
About Dr Anna Dorothea Wagner
Anna Dorothea Wagner MD, graduated from Freie Universität Berlin in 1994 and is trained in Internal Mediicne, Hematology and Oncology at Martin-Luther University Halle Wittenberg and University of Jena, Germany.
Since 2008 she has been working as Cheffe de Clinique at the Cancer Center of the University of Lausanne, Switzerland, where she is currently responsabe for GI medical oncology.