The San Antonio Breast Cancer Symposium was held December 6-10, 2011. Each year, this meeting brings together approximately 8,000 clinicians and scientists who focus on breast cancer. The meeting this year was not only well attended, but highlighted data that were particularly exciting. With few exceptions, my colleagues and I came away from the meeting feeling as though real progress is being made. Many of the preclinical findings (work done in laboratory settings in either cells or animals) were of great interest, and there were several clinical presentations that have the potential to affect and change clinical practice. I will highlight some of the most important findings below.
Everolimus for the treatment of metastatic breast cancer
The drug everolimus is an mTOR inhibitor, a class of targeted therapy drugs (a treatment that is focused on a specific molecular pathway in cancer cells) under study as a way to increase the benefit of hormone therapy (such as aromatase inhibitors). For patients with estrogen receptor positive metastatic breast cancer, the BOLERO (Breast Cancer Trials of Oral Everolimus) study demonstrated everolimus in combination with the aromatase inhibitor exemestane slowed the growth of tumors better than exemestane alone. This study was conducted in multiple countries around the world and included women whose cancer had previously progressed (grown) on treatment with an aromatase inhibitor (either anastrozole or letrozole).
Women were randomly assigned to treatment with exemestane plus everolimus or exemestane alone. Women who received the combination of exemestane plus everolimus experienced a much longer time until the cancer progressed (worsened). The median difference in time to progression between the two groups was about five months, and for some women in the combined treatment group, the time to progression was well over a year.
Everolimus did have added side effects though. Some women developed fatigue, gastrointestinal difficulties, skin rashes and lung problems. At present, everolimus is not approved for use in breast cancer, though it is reasonable to assume the Food and Drug Administration (FDA) will strongly consider an approval. Most clinicians will hold off on using the drug until the approval comes through. Until that time it may be difficult to obtain insurance coverage for everolimus, which is an expensive oral medication.
Perhaps what is most exciting about the BOLERO study is that it is one of the first to demonstrate a targeted therapy can add benefit to a hormonal therapy. Other similar trials are ongoing and there is every reason to believe similar agents may also be effective.
Pertuzumab for the treatment of metastatic breast cancer
Patients with HER2 positive breast cancer will also have new treatment options available in the months ahead. Pertuzumab is a new targeted antibody therapy that, like trastuzumab (another targeted antibody therapy), binds to the HER2 receptor. However, pertuzumab works differently from trastuzumab.
The CLEOPATRA (Clinical Evaluation of Pertuzumab and Trastuzumab) trial compared pertuzumab in combination with trastuzumab and chemotherapy (with docetaxel) to trastuzumab and chemotherapy alone in women with metastatic HER2-positive breast cancer. When pertuzumab and trastuzumab were given together with chemotherapy, they were considerably more effective than treatment with chemotherapy plus trastuzumab alone. The median improvement in progression-free survival was approximately six months, and this improvement was achieved with only a small increase in side effects. There was also the suggestion that the addition of pertuzumab may extend a woman’s life, but these are early findings and final conclusions about survival are still pending.
It is very likely the CLEOPATRA study will lead to the approval of pertuzumab by the FDA for patients with metastatic HER2 positive breast cancer. Assuming the FDA provides an approval, the combination of pertuzumab, trastuzumab and chemotherapy will become a standard treatment for HER2-positive metastatic breast cancer.
As many would suspect, pertuzumab is likely to be quite expensive. With cost in mind, it is going to be important to sort out whether some patients can do as well with trastuzumab and chemotherapy alone, perhaps saving the pertuzumab until somewhat later in the course of the disease. At the present time, pertuzumab is only available as part of a clinical trial (and it is unlikely to be available outside of a clinical trial for at least another six to nine months).
A large trial is underway in women with HER2-positve early breast cancer to see whether treatment with pertuzumab in combination with trastuzumab and chemotherapy can lower the risk of recurrence compared to treatment with trastuzumab and chemotherapy alone.
Bevacizumab in the treatment of metastatic breast cancer
The Averel trial results were one of the disappointments of the meeting. This study looked at adding bevaciuzmab (Avastin) to trastuzumab-based therapy in women with HER2-positive metastatic breast cancer. Although there was a small improvement in progression-free survival, the benefit was quite small and there was no improvement in overall survival (it did not extend life). At this time, it does not appear there is (or will be) a role for bevacizumab in the treatment of HER2-positive metastatic breast cancer.
Ductal carcinoma in situ
Finally, a new test was presented which was designed to help identify women with ductal carcinoma in situ (DCIS) who may not need any treatment other than surgery. The test, called the DCIS Recurrence Score, was developed by Genomic Health in conjunction with a number of academic partners. Although most breast cancer experts agree we over-treat a number of women with DCIS, there have been no reliable methods available to determine which patients are at the lowest risk (the best candidates for a minimal treatment approach). The DCIS Recurrence Score attempts to identify these low-risk patients, but the test has only been used in a limited pool of patients. At this time, most breast cancer experts believe further data are needed before we can apply the DCIS Recurrence to routine clinical practice.
Once again, the SABCS meeting was highly productive and very stimulating. Hopefully next year’s meeting will be every bit as promising. Although the pace of advances seems slow (both to you and me), there is no question that advances are coming.
Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone receptor-positive advanced breast cancer. NEJM. December 7, 2011 [Epub].
Baselga J, Cortés J, Kim S, et al. for the CLEOPATRA Study Group. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. NEJM. December 7, 2011 [Epub].