Archive for the ‘Breast Cancer’ Category

New Treatment for Her-2+ Metastatic Breast Cancer Opens at CORT

September 4, 2009

CORT has opened the Wyeth 3144A2 3005 WW Study testing the oral her-2 inhibitor, neratinib, in combination with paclitaxel (Taxol), versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. 

Neratinib is an oral anti-her-1/her-2 drug with demonstrated efficacy in metastatic her-2 positive breast cancer.  The safety studies have demonstrated acceptable and manageable toxicity of neratinib, including rash and occasional loose stools or diarrhea being most common.  As with other her-2 inhibiting drugs, neratinib may lower the cardiac ejection fraction, so serial monitoring of cardiac function is routine.  The Phase III study will compare the efficacy and tolerability of paclitaxel with either oral neratinib or trastuzumab (a monoclonal antibody against her-2 protein, given IV).

The potential advantages of neratinib include improved convenience (and possibly improved safety).  The drug is given orally.  

For more information about this study, visit our website at www.CORTPA.com, or contact a Research Coordinator at 972-566-5588.  

Patients with her-2+ breast cancer may also be eligible for other studies and treatment at CORT, including non-study therapy.  The principle investigator at CORT is Dr. Barry Mirtsching.  He has personally conducted over 200 trials in cancer therapy over 16 years, many in breast cancer management.  Experience in both trial and non-trial breast cancer management benefits patients by producing better treatment outcomes.  Care at CORT is individual and personal, with adequate time for problem-solving and direct contact with the physician.

STRIDE Breast Cancer Study Testing Stimuvax Cancer Vaccine Open at CORT

September 4, 2009

CORT has opened the STRIDE study for first-line treatment of metastatic, hormone-receptor positive breast cancer.  The study will test standard anti-estrogen therapy in combination with a vaccine placebo, versus standard anti-estrogen therapy with the Stimuvax cancer vaccine.  The press release regarding this study is posted below.

For more information about this study, or to schedule appointments for evaluation and treatment of metastatic breast cancer, visit the CORT website at www.CORTPA.com, or call 972-566-5588 and ask to speak with a Patient Care Coordinator or CORT Research Nurse. 

STRIDE Press Announcement:

24 Jun 2009 – Merck KGaA announced the initiation of its global Phase III clinical study of the therapeutic cancer vaccine Stimuvax® (BLP25 liposome vaccine, L-BLP25) in patients with advanced, inoperable breast cancer. The STRIDEa study will determine if Stimuvax can extend progression-free survival in patients treated with hormonal therapy who have hormone receptor-positive, locally advanced, recurrent or metastatic breast cancer. Overall survival, quality of life, tumor response and safety will also be assessed in this study. The STRIDE study will be supervised by an expert Steering Committee and is sponsored by Merck, which is leading the development of Stimuvax.
STRIDE will enroll more than 900 patients with advanced breast cancer at an estimated 180 sites in over 30 countries – within North America, Europe, Asia and Australia; the Principal Investigator is Dr Lawrence Shulman, Chief Medical Officer and Senior Vice President for Medical Affairs, Dana-Farber Cancer Institute, Boston, USA.
 
Stimuvax is an investigational therapeutic cancer vaccine designed to stimulate the body’s immune system to identify and target cancer cells that express MUC1, an antigen commonly expressed in breast cancer as well as in other common cancer types such as non-small cell lung cancer (NSCLC), multiple myeloma, and colorectal, prostate and ovarian cancers.
 
The Phase III program for Stimuvax was initiated following results from a randomized Phase IIb study of 171 patients with inoperable stage IIIb NSCLC, in which Stimuvax showed a trend towards extending median overall survival from 13.3 months for patients receiving best supportive care (BSC) to 30.6 months for patients receiving Stimuvax plus BSC. Reported side effects included mild-to-moderate flu-like symptoms, gastrointestinal disturbances and mild injection-site reactions. A further long-term safety analysis in 16 patients receiving prolonged treatment with Stimuvax from 2 to 8.2 years showed the most common treatment-related adverse events were injection-site reactions (ISRs) with no evidence of autoimmune reactions. These data also show that the occurrence of ISRs decreased with long-term therapy (>1 year).

CORT Raising Funds for Susan Komen in Race-for-the-Cure

August 8, 2009

Dear Friends,

CORT has recently accepted the challenge to raise funds to support the 2009 Komen Dallas Race for the Cure®  on October 17th. 

Please join us in the fight by donating in support of my participation in the Race.  Your tax-deductible contribution will fund local outreach and awareness programs for underserved communities in the Dallas County area and national breast cancer research.

Donating is quick and easy.  Click here to visit my personal page and pledge your support.  If you would prefer you can mail a check or money order to my attention to the address below.  No donation is too small.  I truly appreciate your support.

Sincerely,

Barry Mirtsching
7777 Forest Land B242

Dallas, TX 75230-2525
 

To sponsor my participation online, click here.

Study Tests Extension of Anti-Her-2 Therapy Beyond Herceptin for Early Stage Breast Cancer Patients

August 5, 2009

The Wyeth Study 3144A2-3004-WW testing a new oral drug, neratinib, is active and enrolling at CORT.  This study is open to early-stage, her-2 positive patients who have completed adjuvant therapy and one year of trastuzumab (Herceptin), the current standard-of-care.  Such patients are generally followed without further treatment.  The relapse risk of these patients is reduced by the one year of trastuzumab (see Figure 1: Analysis of Relapse Risk over Time, adapted from Herceptin Product Literature).  

Annual Relapse Risk for Her-2 Positive Early-Stage Breast Cancer Patients, Treated with or without Trastuzumab

As can be seen from the figure, the AC>TH arm has a lower risk of annual recurrence that begins during the first year (the time the treatment with trastuzumab is given), and that benefit continues, when compared to patients treated with chemotherapy alone (AC>T).  However, the risk for recurrence does rise in the trastuzumab-treated patients after the therapy is completed at one year, and that risk remains increased for another 2 or 3 years, at approximately 4.9% per year. 

To address that continued risk, studies testing the extension of anti-her-2 therapy are being conducted.  The Wyeth study at CORT tests the oral anti-her-2 drug neratinib (HKI-272).  The study is a randomized comparison of neratinib versus a neratinib placebo, given daily by mouth for one year.  Neratinib may reduce cardiac function (similar to other her-2 blockers), so function must be monitored.  Other risks include rash, diarrhea, and nausea.  Based on experience with the drug to date, these risks can be managed with supportive care medication and/or dose reduction in most circumstances. 

Patients who have completed one year of adjuvant therapy with trastuzumab (Herceptin), and who are within 2 years of completion of that therapy are eligbile for the Wyeth study at CORT. 

For more information about this study, or to schedule a consultation about management of breast cancer, call 972-566-5588, and ask to speak with a Patient Care Coordinator.   Additional information about this study, and directions to the office are located at: www.CORTPA.com.

First-Line Chemotherapy for Her-2 Negative Metastatic Breast Cancer

January 12, 2009

Paclitaxel (Taxol) chemotherapy in combination with Bevacizumab (Avastin) has become a standard treatment regimen for her-2 negative patients with metastatic breast cancer, based on findings of improved outcomes with the combination in the ECOG 2100 study.  That trial  compared paclitaxel alone to paclitaxel and bevacizumab combination therapy.  For the combination, response rate was improved (30% vs. 14%, p<0.0001) and progression-free survival was improved (11.4 mos. vs. 6.1 mos; HR=0.51, p<0.0001).  Bevacizumab was approved for treatment of metastatic breast cancer based on these results. 

Many patients may not be appropriate for the combination of paclitaxel and bevacizumab therapy.  Patients who have received prior taxane therapy in the adjuvant setting (particularly with a short disease-free interval to the time of metastatic disease) may increased risk for resistance to taxane therapy.  Patients who are diabetic may have exacerbation of diabetes because of corticosteroid premedication required before taxane therapy.  Patients with neuropathy may have worsening of neuropathy with taxane therapy.  

For these patients,  therapy with another chemotherapy agent in combination with bevacizumab may be considered.    However, clinical trial data supporting the combination of other chemotherapy agents with bevacizumab is limited, and insurer coverage may be restrictive.   An example of an alternative regimen would be gemcitabine (Gemzar) and bevacizumab.   No corticosteriod premedications are required for gemcitabine therapy, and there is no risk of neuropathy. 

Other important clinical circumstances may make the use of bevacizumab unattractive, such as severe hypertension, angina or recent ischemic events from coronary or cerebrovascular disease, thrombosis risk, bleeding, or the presence of CNS metastatic disease.  Bevacizumab may cause proteinuria, increased blood pressure, bleeding, thrombosis, infusion reactions, delayed wound healing, or other rare toxicities (bowel perforation). 

For more information about breast cancer therapy and clinical trial information, contact a CORT Research Coordinator at 972-566-5588 (Dallas) or 972-981-4012 (Plano), or visit our website at www.CORTPA.com.

TDM1 (Trastuzumab-DM1) Immunoconjugate Drug Therapy Study Open at CORT

December 10, 2008

A phase III study of Trastuzumab-DM1 for treatment of relapsed her-2 positive metastatic breast cancer is open at CORT. 

Trastuzumab (Herceptin)  is a monoclonal antibody against the her-2 protein, which is overexpressed or amplified in an aggressive subset of breast cancers.  Trastuzumab and chemotherapy combination therapy has substantially improved response, progression-free survival, and overall survival of metastatic her-2 positive breast cancer patients.  Trastuzumab is approved for treatment of metastatic breast cancer.  Trastuzumab may be associated with uncommon infusion reactions and myocardial dysfunction, which may produce clinical congestive heart failure in about 1% of patients, which may be reversible in some cases with discontinuation of therapy.  When her-2 positive metastatic breast cancer progresses on a first-line trastuzumab + chemotherapy regimen, continuing trastuzumab (or another anti-her-2 drug) in the second-line treatment setting (with a different chemotherapy drug) is beneficial with regard to response and stopping disease progression (compared to therapy with chemotherapy alone). 

Lapatinib (Tykerb) is an oral drug that inhibits the intracellular, activating portion of the her-2 molecule.  It has been approved (in combination with capecitabine (Xeloda)) for treatment of metastatic her-2 positive breast cancer that has progressed after trastuzumab-based initial therapy. 

Trastuzumab-DM1 (TDM1) is a drug that combines trastuzumab with a linked chemotherapy agent, maytansine (DM1).   This linkage of an antibody and a drug is termed an immunoconjugate.  The potential advantage of immunoconjugate therapy is that the antibody targets DM1 specifically into tumorous tissue, which may reduce the toxicity of treatment.   In addition, the antibody trastuzumab has it’s own anti-cancer activity.  TDM1 has been tested in open-label phase I and II studies, with mild toxicities and effectiveness, even in heavily pre-treated her-2 positive metastatic breast cancer.  Adverse events that have been noted include elevated liver function tests, fatigue, anemia, and thrombocytopenia. 

The Phase III study at CORT is part of a large multicenter national study.  The study will test the activity of trastuzumab-DM1 versus standard therapy (lapatinib-capecitabine) for second-line therapy of patients with metastatic her-2 positive breast cancer.

For more information about this study, consultation, or referral, contact a CORT Research Coordinator at 972-566-5588, or visit our website at www.CORTPA.com.

ALLTO Study Evaluates the Role of Lapatinib (Tykerb) in Adjuvant Therapy of Her-2 Positive Breast Cancer

November 10, 2008

CORT has opened the NCCTG N063D (BIG 2-06) study for adjuvant therapy of her-2 positive breast cancer.  This study is a worldwide study funded by the National Cancer Institute Cooperative Group (NCCTG).  It is known as the ALLTO study

Her-2 (ErbB-2) is a protein which can drive the growth of breast cancer.   It is overexpressed on the cancer cell surface in as many as 25% of breast cancers.  That expression is a result of amplification of the Her-2 gene in those cases.  Standard adjuvant therapy for her-2 positive breast cancer includes treatment with chemotherapy and trastuzumab (Herceptin).  Trastuzumab is a monoclonal antibody that blocks her-2 protein on the cancer cell surface.  Several studies (NSABP B-31, NCCTG N9831, FinHer, BCIRG 006) established the role of adding trastuzumab to adjuvant chemotherapy, with significant (50%) relative risk reduction in the recurrence risk of disease recurrence.  At the present time, standard therapy may consist of a sequence of doxorubicin (Adriamycin) and cyclophosphamide (AC), followed by taxane therapy, with trastuzumab given during the taxane portion of that treatment.  In addition, trastuzumab therapy is given as maintenance for a duration of one year. 

The ALLTO study compares the effectiveness of another anti-her-2 drug, either alone or in combination with trastuzumab.  That drug is lapatinib (Tykerb).  Lapatinib is an oral drug.  Lapatinib has a different mode of blocking the her-2 protein.  Lapatinib binds the intracellular (inside the cell) portion of the her-2 molecule, stopping the action her-2 from activating other signaling proteins in the cell.  Lapatinib is approved in combination with chemotherapy (capecitabine=Xeloda) for treating metastatic breast cancer that has progresed after at least one trastuzumab-chemotherapy combination therapy.  The ALLTO study is moving lapatinib therapy into the adjuvant treatment setting.

There are two treatment designs in the ALLTO study.  The physician will select the treatment design that he feels most appropriate for the patient’s care.  Patients in group 1 (design 1) will complete all of their chemotherapy before starting anti-her-2 therapy.  Patients in group 2 (design 2) will complete standard AC therapy, and then have standard weekly paclitaxel (Taxol) therapy.  In group 2, the anti-her-2 therapy will begin at the same time as the initiation of paclitaxel therapy.  In both groups, the patients will be randomized between four anti-her-2 treatments: 1) lapatinib daily for one year, 2) trastuzumab for one year, 3) trastuzumab for 12 weeks, followed by 6 weeks of no therapy, then lapatinib for 34 weeks, and 4) lapatinib and trastuzumab for 52 weeks.  The schema for design 2 is depicted below.

altto-study-schema-design-2

Efficacy, safety, and tolerability will be evaluated.

For more information about the ALTTO study, visit the CORT website at www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588 (Dallas), or 972-981-4012 (Plano).

ABCSG-12: Zoledronic Acid (Zometa) Reduces Recurrence of Early Breast Cancer

November 5, 2008

The Austrian Breast and Colorectal Cancer Study Group Trial 12 results were reported at the American Society of Clinical Oncology (ASCO) 2008 Annual Meeting.  The study compared treatment with zoledronic acid (Zometa) with placeo in premenopausal women who were treated with anti-estrogen therapy following surgery. 

Between 1999 and 2006, over 1800 women participated in the study. All were premenopausal, had estrogen receptor (ER)- and/or progesterone receptor (PR)-positive stage I or II (<10 positive nodes) breast cancer, and have received no chemotherapy other than neo-adjuvant (pre-operative) treatment.

Following completion of surgery (with radiotherapy in breast conservation cases), women were treated with 3.6 mg of goserelin (an ovarian suppression LHRH drug) and then randomized to one of four treatment arms: tamoxifen 20 mg/day; tamoxifen 20 mg/day plus zoledronic acid 4 mg given intravenously every 6 months; anastrozole 1 mg/day; or the AI plus the bisphosphonate at the same doses and schedule.

Dr. Gnant of the University of Vienna reported that the disease-free (DFS) and overall survival (OS) rates were very good for the whole cohort, at 94.0% and 98.2%, respectively.

A total of 137 first DFS events were reported. Of these, 72 occurred in patients treated with anastrozole, and the remaining 65 occurred in those treated with tamoxifen. Statistical analysis showed no significant difference in the primary endpoint of DFS according to the type of endocrine treatment used, but there was a significant difference according to whether or not patients had been given the bisphosphonate. Of the 137 DFS events, 54 occurred in women who had received zoledronic acid, with the remaining 83 in those who had not received the drug. This gave a hazard ratio of 0.643 (95% confidence interval: 0.46-0.91), with a p value of 0.011, in favor of bisphosphonate use over no bisphosphonate use.  This is a 35% reduction in the number of events. 

The reduction in events were not limited to bone metastasis reduction.  Reduction in other distant metastases, local recurrence, and contralateral breast cancer events was established. 

Zoledronic acid is a bisphosphonate drug which reduces bone resorption and thereby increases bone mineral density.  Bisphosphonates are approved therapies for treatment of osteoporosis.   The anticancer effect of bisphosphonates has been suggested in prior studies of other bisphosphonate drugs, e.g., oral clodronate (NSABP).  The mechanism of the anticancer effect is not known. 

These results have been called “practice changing” by some observers, but not all.  However, if the effect is confirmed in other large ongoing studies (AZURE, BIG 1-04, NATAN, GAIN, NSABP B-34), then the use of bisphosphonate therapy is likely to have a large impact on practice, as well as the design of future studies. 

Access to bisphosphonate therapy for adjuvant therapy of early breast cancer in the US is limited, because the drugs are not FDA-approved yet for breast cancer treatment.  For example, Medicare does not pay for coverage for zoledronic acid for breast cancer.  Private payors may not pay for zoledronic acid for breast cancer either, since their treatment algorithms heavily rely upon national guideline groups and current FDA approvals.  While zoledronic acid is approved for osteoporosis, the dosing of the drug at the approved frequency is yearly, and the dosing that was shown to be effective in the ABCSG study was more frequent, so therapy was more intensive. 

Patients may gain access to bisphosphonate therapy for early breast cancer by enrolling in clinical studies, such as the SWOG S0307 Study which is open at CORT.  This study compares the efficacy of three different bisphosphonate drugs (IV zoledronic acid, oral clodronate, oral ibandronate) in a randomized fashion.  All patients will receive one of the bisphosphonate therapies.  Three is no placebo group.  This study will also include a broader range of patients, including pre- and post-menopausal women, ER- and ER+ disease, and those who have receive either pre- or post-operative chemotherapy.  In addition, the use of adjuvant biologic therapy such as trastuzumab (Herceptin) or bevacizumab (Avastin) is allowed.  For more information about this study, visit the CORT website (www.CORTPA.com), or call 972-566-5588 to speak with a Study Coordinator.

Addendum (2/12/09):  The ABCSG-12 Study Results were published in the New England Journal of Medicine today.  The reference is: Gnant, M. et al., NEJM 2009; 360 (7): 679-691. 

Abraxane (nab-paclitaxel) with or without Herceptin in First-Line Treatment of Metastatic Breast Cancer: ION 04-012 Study Results from the ASCO 2008 Annual Meeting

June 12, 2008

The International Oncology Network (ION) Study 04-012 results were presented in a poster presentation at the ASCO 2008 Annual Meeting.  This study was an open label Phase II study of Abraxane (nab-paclitaxel) therapy at 125 mg/M2 weekly for three out of four weeks, cycles every 4 weeks for first-line treatment of patients with metastatic breast cancer.  Patients with her-2 overexpressing or amplified disease also received Herceptin on a standard weekly schedule. 

This is a copy of the poster:

04-012-asco-poster-5-20-08

Abraxane is a protein-bound paclitaxel formulation, which can be given over shorter infusion duration than other taxanes, and it has a low rate of allergy or infusion reactions because it is cremaphor solvent-free.  Abraxane infusions do not require steroid premedication.   In previous studies of Abraxane in metastatic breast cancer, encouraging activity has been noted, even in pre-treated patient groups.  The response rate seen with Abraxane in other studies appears to be comparable or superior to responses seen with other taxane drugs. 

The ION Study enrolled 72 patients.  At the time of the analysis, 47 were evaluable for response.  There were 29 her-2 negative patients and 17 her-2 positive evaluable patients.  One patient had her-2 unknown status.  In the her-2 negative group, there were 9 partial responses (31%) and 18 (62%) patients with stable disease.  In the her-2 positive group, there were 2 complete responses (12%), 9 partial responses (53%), and 5 (29%) patients with stable disease.   Therefore, the overall response rate in her-2 positive patients was 65%.   Overall, for all patients, the response rate was 43%.  Median time to progression was 15.9 months, and median overall survival was 25 months.

Treatment was well tolerated and grade >=3 toxicities were mostly limited to neutropenia and/or fatigue.  Infections were uncommon. 

Dr. Barry Mirtsching of CORT was the Principle Investigator of this study.   Special thanks to Abraxis Oncology, the many ION investigator physicians, study coordinators, and participating patients who helped make this research study possible.  

ION is continuing to study Abraxane therapy in the setting of metastatic breast cancer.  Dr. Mirtsching at CORT is also the Principle Investigator for the study of Abraxane and Sorafenib (Nexavar) for first-line therapy of metastatic breast cancer.  Sorafenib is an oral drug with anti-angiogenic activity.  It is approved for the treatment of metastatic renal (kidney) cancer.  The combination of anti-angiogenic drugs and taxane therapy has shown promise in treatment of metastatic breast cancer.  Bevacizumab (Avastin), a monoclonal antibody with anti-VEGF (vascular endothelial growth factor) activity, and paclitaxel has been shown to improve progression-free survival when compared to paclitaxel alone.  Sorafenib would be a significant advance for breast cancer patients if it proves to be as active as Avastin, because it is oral and has a generally more favorable toxicity profile than Avastin.  Abraxane was chosen in this study for the clinical advantages noted previously.

For more information about the ION 06-025 Study of Abraxane and Sorafenib, please call 972-566-5588 (Dallas), or 972-981-4012 (Plano), or visit the www.CORTPA.com

Bisphosphonate (Zoledronic Acid=Zometa) Improves Adjuvant Endocrine Therapy for Pre-menopausal Breast Cancer Patients; Ongoing CORT Study Assesses Bisphosphonates in Adjuvant Therapy in Broader Groups of Patients

June 6, 2008

Here is the ASCO (American Society of Clinical Oncology) News Post regard the Zoledronic Acid (Zometa) study presented at the ASCO 2008 Annual Meeting, demonstrating improved outcomes for pre-menopausal breast cancer patients receiving adjuvant endocrine therapy:

Zoledronic Acid Added to Endocrine Therapy Improves Outcome for Premenopausal Patients with Early Breast Cancer

 

Zoledronic acid has been found to increase disease-free survival by 36% and relapse-free survival by 35% for premenopausal patients who received adjuvant endocrine therapy for early breast cancer (Abstract LBA4). Michael Gnant, MD, of the Medical University of Vienna, Austria, presented the data on behalf of the Austrian Breast and Colorectal Cancer Study Group (ABCSG) during Sunday’s Plenary Session.

Adjuvant endocrine therapy with ovarian suppression is used as an effective alternative to standard cytotoxic chemotherapy for premenopausal patients with endocrine-responsive breast cancer. ABCSG-12 is the first study to compare endocrine suppression with goserelin plus tamoxifen to goserelin plus an aromatase inhibitor (anastrozole).

Adjuvant bisphosphonate therapy (zoledronic acid) was included in two of the four treatment arms both to mitigate the marked bone loss associated with complete ovarian suppression and to explore whether the antitumor effects demonstrated previously in preclinical and clinical settings might translate into a longer time to disease recurrence and improved survival.

The study was a randomized, open-label, phase III, modified 2×2, four-arm trial of oral tamoxifen and goserelin with or without zoledronic acid compared with oral anastrozole and goserelin with or without zoledronic acid for 3 years.

The primary endpoint of this trial was disease-free survival for the 903 patients who received anastrozole compared with the 900 patients who received tamoxifen. Secondary endpoints included overall survival and the effect of the treatments on local-regional relapse. The effect of treatment on bone metastasis-free survival was considered to be an exploratory endpoint.

At a median follow-up of 60 months, overall 5-year disease-free survival was 94% and overall survival was 98.2%. No difference in disease-free survival was detected among patients who received tamoxifen and those patients who received anastrozole. There was no advantage in relapse-free or overall survival rates for anastrozole over tamoxifen.

In the analysis of zoledronic acid, the bisphosphonate improved the primary endpoint of disease-free survival (hazard ratio [HR] = 0.643, p = 0.011). The incidences of contralateral breast cancer, distant metastases, and local-regional recurrence were all reduced by zoledronic acid (six vs. 10 cases, 29 vs. 41 cases, and 10 vs. 20 cases for the group treated with zoledronic acid compared with those patients who were not treated, respectively). Forest plots showed that the effect for all subgroups clustered around the main effect with no interaction. Treatment with zoledronic acid increased relapse-free survival (HR = 0.653, p = 0.014), with a trend toward improvement in overall survival (HR = 0.595, p = 0.101).

Zoledronic acid treatment was well tolerated. No renal toxicity or confirmed cases of osteonecrosis of the jaw occurred. Differences in side effects among the tamoxifen and anastrazole groups were seen. Arthralgia, bone pain, and fever were more frequent (all, p < 0.0001) in the anastrozole groups, especially for those patients who received zoledronic acid. The only serious adverse events that reached statistical significance included an increased incidence of uterine polyps (p < 0.0001) and thrombosis (p = 0.012) in the tamoxifen groups.

Dr. Gnant noted that differences in efficacy between tamoxifen and anastrozole may not have been detectable because of the effect of goserelin on suppression of ovarian function and that perhaps two large ongoing studies will provide better answers. The Suppression of Ovarian Function Trial (SOFT) has enrolled 3,000 patients, and the Tamoxifen and Exemestane Trial (TEXT) has enrolled 1,845.

With regard to zoledronic acid, Dr. Gnant said, “Zoledronic acid significantly improves clinical outcomes beyond those achieved with endocrine therapy alone.” The benefit was seen in and outside of bone (reduction in contralateral breast cancers, local-regional recurrence, and distant nonbone metastases) with acceptable toxicity. Dr. Gnant concluded that adjuvant therapy with zoledronic acid should be considered in order to improve the standard of care for premenopausal women, although the optimal dose, schedule, and treatment duration are yet to be addressed.

Discussant Martine J. Piccart-Gebhart, MD, PhD, of Jules Bordet Institute — Université Libre de Bruxelles, Belgium, referred to ABCSG-12 as elegant in design, but also noted some of its limitations: the study was not double-blind, the control arm (goserelin plus tamoxifen for 3 years) is not widely accepted, and there was no stratification for HER2. Another important observation was that the large confidence interval of the hazard ratio for disease-free survival comparing tamoxifen and anastrozole (HR = 1.096; 95% CI; 0.78, 1.53) suggests that this study was not adequately powered to detect a 20% difference between the two drugs. Dr. Piccart-Gebhart noted that the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (Howell A, et al. Lancet. 2005;365[9453]:60-62) and the Breast International Group (BIG) 1-98 (Thurlimann BJ, et al. Abstract 511. Presented at: 2005 ASCO Annual Meeting) were powered to detect a 20% difference in disease-free survival between tamoxifen and an aromatase inhibitor. ATAC required 6,241 patients and 900 events, and BIG1-98 required 4,922 women and 770 events.

With regard to the zoledronic acid results, Dr. Piccart-Gebhart suggested that the data illustrate the 1889 “seed and soil” hypothesis of Paget (Paget S. Lancet. 1889;1:571-573), that is, zoledronic acid affects not only malignant cells (the “seed”), but also the tissues in which metastases grow (the “soil”). Dr. Piccart-Gebhart concluded that ABCSG-12 is not yet a practice-changing trial, but an important trial, “announcing a paradigm shift: targeting both seed and soil.”

END OF ASCO POST

The SWOG (Southwest Oncology Group) S0307 Study open at CORT continues enrollment.  This study evaluates the addition of one of three bisphosphonate drugs (Zoledronic Acid, Clodronate, or Ibandronate) in adjuvant therapy of breast cancer.  Patients with Stage I-III resected breast cancer are eligible.  They may have received chemotherapy and/or hormonal therapy.   ER+ and ER- patients are eligible.  The study enrolls pre- and post-menopausal patients. 

For more information about this study, call 972-566-5588 (Dallas) or 972-981-4012 (Plano), and ask to speak with a research coordinator.  More information about CORT and CORT studies is available at www.CORTPA.com.