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Hi Everyone,
Here is the interview with Dr. Perez that was featured in Medscape a few says ago:
From Medscape Hematology-Oncology
Expert Interview
Advances in Targeted Therapy for Women With Breast Cancer: An Expert Interview With Dr. Edith Perez
Editor's Note:
More than 200,000 new cases of breast cancer are diagnosed in the United States each year.[1] The majority of patients are diagnosed with early-stage disease and greater than 80% are expected to live 5 years or longer with current therapies.[1] From 25% to 30% of patients with early-stage breast cancer have tumors that are positive for the HER2-neu growth factor receptor.[2] Historically, these patients have more aggressive cancers and a higher risk for cancer recurrence. Trastuzumab is a monoclonal antibody directed against the HER2 receptor that has been shown to improve outcomes, including survival, for patients with metastatic HER2-positive disease.[2] The role of trastuzumab in adjuvant therapy for early-stage disease has been the subject of several large multicenter randomized controlled trials.
The preliminary results of these studies were presented and discussed during a special afternoon session at this year's American Society of Clinical Oncology meeting. The data from the joint analysis of NSABP-B-31 and NCCTG-N9831, as well as preliminary data from the HERA trial, suggest that adjuvant trastuzumab can markedly decrease the risk of recurrence for patients with HER2-positive early-stage breast cancer.[3-5] On behalf of Medscape, Dr. Jeffrey Peppercorn, of the Dana-Farber Cancer Institute in Boston, discussed these findings with Dr. Edith Perez, Professor of Medicine and Codirector of the multidisciplinary breast clinic at the Mayo Clinic, Jacksonville, and Chair of the NCCTG breast committee.
Medscape: Dr. Perez, today you and your colleagues presented exciting results from clinical trials of adjuvant trastuzumab for patients with HER2-positive breast cancer.[3-5] Can you explain the significance of this study?
Dr. Perez: These results were exciting and very meaningful for patients with HER2-positive invasive breast cancer. Data from the NCCTG N9831 Intergroup trial combined with data from NSABP B-3[3] demonstrated a 52% reduction in risk of breast cancer recurrence as well as a 33% survival benefit with adjuvant trastuzumab therapy. These results were supported by the findings of the HERA trial[5] of adjuvant trastuzumab, which found a 46% reduction in recurrence by adding trastuzumab to chemotherapy. This information changes the standard of care for patients with HER2-positive breast cancer irrefutably.
Medscape: All of these trials administered trastuzumab in different regimens and schedules. Do we now know the best way to give trastuzumab in the adjuvant setting?
Dr. Perez: We don't. I believe the earlier we use Herceptin [trastuzumab], the better the outcomes will be. The disease-free survival curves in our trial started separating early. I think that for women who have either node-positive or node-negative breast cancer, we really need to think about moving Herceptin use as early in treatment as possible, rather than giving the tumor a chance to relapse. The data from our NCCTG N9831 suggest that concurrent therapy with paclitaxel may be better than waiting to add the Herceptin until after the paclitaxel, but more follow up is needed before we can reach definite conclusions.
Medscape: Your trial included all patients with HER2-positive breast cancer and positive lymph node involvement as well as high-risk HER2-positive patients with negative lymph nodes. Given the benefit seen in these studies, do you think adjuvant Herceptin should be considered for patients with negative lymph nodes and tumors that would have been too small for inclusion in your study?
Dr. Perez: Our NCCTG N9831 trial enrolled patients with negative lymph nodes and tumors 1 cm or greater with estrogen receptor-negative disease and 2 cm or greater with estrogen receptor-positive disease. This eligibility criteria was somewhat arbitrary, so at this time I would not limit the therapy based on tumor size. Anyone who has a HER2-positive invasive breast cancer is a candidate for this therapy.
Medscape: How was adjuvant Herceptin tolerated in your study?
Dr. Perez: Very well. The only issue was a low possibility of cardiac events. Otherwise, there was no nausea, no vomiting, no hair loss. It was well tolerated.
Medscape: How should the cardiac toxicity be monitored in practice?
Dr. Perez: I think patients should be monitored as they were in the clinical trial. Left ventricular ejection fraction should be evaluated before starting therapy. In the trial, we repeated assessment of ejection fraction every 3 months and then 6 months. This is particularly important for the first year of therapy. After that time, the best way to monitor is unknown. In the beginning, for that first year, we must be very careful.
Medscape: How should clinicians approach patients with HER2-positive disease who have completed adjuvant therapy without trastuzumab?
Dr. Perez: This is something we are looking at. Based on the natural history of breast cancer, where we see the disease-free survival curves continue to decrease, this therapy is going to have to be considered for women who have completed chemotherapy. I don't think those women will derive as great a benefit as those who are treated with trastuzumab combined with chemotherapy, but it should be considered for these patients -- ideally, we should conduct a trial to quantitatively assess whether there is a meaningful benefit in this situation.
Medscape: How did you decide to study 1 year of trastuzumab, instead of a shorter or longer duration of therapy?
Dr. Perez: We could have selected 6 months, but based on preclinical models, we knew we had to use it for a long time. We felt that if we required 2 years of therapy, we might run into problems with compliance. We felt that 6 months might be insufficient duration, but it was a somewhat arbitrary decision. We are currently working on a new clinical study to evaluate the optimal duration of therapy.
Medscape: We have also recently heard exciting results about treatment with bevacizumab for patients with metastatic breast cancer.[6] Do you think bevacizumab will have a role in adjuvant therapy as well?
Dr. Perez: It has to be looked at. The safety profile will need to be considered carefully. This looks most appealing now for HER2-negative patients, but studies in patients with HER2-positive disease are ongoing. In terms of an adjuvant trial, we need to determine whether the combination of trastuzumab and bevacizumab will be beneficial. There is an ongoing small phase 1 study evaluating safety, and phase 1/2 trials are needed. So at this time, we are optimistic about this being an important avenue for research, but not one that is ready for general clinical practice.
Medscape: What do you see as the future directions for the care of HER2-positive patients?
Dr. Perez: I see a better life for patients with HER2-positive breast cancer. We are looking for ways to combine targeted agents against HER2 because this may take us to the next level.
One thing I would like to clarify is that I would not advise using the combination of the taxane carboplatin and trastuzumab as the sole adjuvant regimen for patients at this time, as we do not have efficacy data for this combination. Anthracyclines may be important for outcome in these women with HER2-positive breast cancer. However, we are awaiting results from a clinical trial (BCIRG 006) that will help to address this question.
Similarly, there are several pilot studies underway looking at the role of adjuvant trastuzumab in dose-dense therapy, and a pilot study of adjuvant trastuzumab with ABI-007. We would not recommend dose-dense therapy with trastuzumab at this time outside of the context of a clinical trial, but pilot studies evaluating safety are already ongoing.
Physicians need to be careful concerning the cardiac toxicity of trastuzumab. We enrolled 3500 women to be able to evaluate the cardiac issues in this setting. Just because you treat 2 patients and they do well or poorly, this does not mean that you can understand the total picture. Our advice is to use the results of this trial, apply the entry criteria, and monitor cardiac effects. Last, but not least, adding trastuzumab to chemotherapy in patients with HER2-positive invasive breast cancer is dramatically better than chemotherapy alone. I hope that all physicians have an opportunity to discuss these new findings with their patients.
Medscape: Thank you very much and congratulations.
Dr. Perez: You're welcome.
References
Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30. Abstract
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:783-792. Abstract
Romond E. Joint analysis of NSABP-B-31 and NCCTG-N9831. Proc Am Soc Clin Oncol. 2005. Late-breaking session.
Perez EA. Further analysis of NCCTG-N9831. Proc Am Soc Clin Oncol. 2005. Late-breaking session.
Piccart-Gebhart MJ. HERA trial. Proc Am Soc Clin Oncol. 2005. Late-breaking session.
Miller KD, Wang M, Gralow J, et al. E2100: a randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer. Proc Am Soc Clin Oncol. 2005. Late-breaking session.
Funding Information
Supported by an independent educational grant from Genentech.
Edith Perez, MD , Professor of Medicine, Division of Hematology-Oncology, Mayo Medical School, Jacksonville, Florida
Disclosure: Jeffrey Peppercorn, MD, MPH, has no relevant financial relationships to disclose.
Disclosure: Edith Perez, MD, has disclosed that she has received grants for clinical research from Bristol-Myers Squibb, Genentech, Eli Lilly, Pfizer, and Roche.
Medscape Hematology-Oncology. 2005; 8 (1): ©2005 Medscape
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