William J. Gradishar, MD, Professor in Medicine-Hematology/Oncology, Northwestern University Feinberg School of Medicine, discusses the treatment of early stage breast cancer with endocrine therapy and considerations following resistance.

A patient with early stage disease who is hormone-sensitive will receive the recommendation to get anti-hormonal therapy, regardless of whether or not they are treated with chemotherapy. The treatment of choice is tamoxifen and an aromatase inhibitor for premenopausal and postmenopausal patients, respectively.

Following treatment, if a patient goes on to develop recurrent metastatic disease, the decision regarding next steps depends on whether or not the patient is premenopausal or postmenopausal and the extent of their disease. Gradishar says that treatment continues as long as the disease remains stable. If it came that the disease was progressing, a physician would go through the same decision tree: considering chemotherapy, alternative endocrine therapies, what the tumor had been exposed to, enrollment on a clinical trial, and an aromatase inhibitor plus mTOR inhibitor. For patients who develop disease progression and remain endocrine-sensitive, a physician would treat with everolimus plus exemestane and continue until disease progression. At that point, a patient would have received most endocrine therapies and chemotherapy would have to be considered.

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Dr. Gradishar on Endocrine Therapy in Early Stage Disease

William J. Gradishar, MD, Director, Maggie Daley Center for Women's Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, describes the need to enrich the patient population in a clinical trial that is investigating a novel targeted therapy.

Gradishar believes that trials investigating novel targeted therapies have the potential to have much higher success rates than traditional clinical trials. Enriching trials based on known driver mutations and pathways, which the treatment is meant to target, drives success and lowers the number of trials that fail.

As an example, Gradishar notes that examining a targeted therapy in 50 tumors with 30 different activated pathways may lower the perceived effectiveness of the targeted agent. However, if a trial is enriched based on a pathway or mutation, the agent will be far more likely to achieve its goal.

William J. Gradishar, MD, from the Northwestern University Feinberg School of Medicine, describes the need to enrich the patient population in a clinical trial that is investigating a novel targeted therapy. 

Dr. Gradishar on Enriching Targeted Therapy Trials

William J. Gradishar, MD, Director, Maggie Daley Center for Women's Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, describes results from the 301 Study that compared eribulin mesylate (Halaven) to capecitabine in patients with locally advanced or metastatic breast cancer following treatment with anthracyclines or taxanes.

In the phase III trial, 1102 patients were randomized 1:1 to receive eribulin or capecitabine as a first-, second-, or third-line treatment. The trial sought to prove that eribulin was superior to capecitabine at improving progression-free survival (PFS) and overall survival (OS), Gradishar notes.

Gradishar explains that when examining the Kaplan-Meier curves from the study a clear overlap between the two arms can be observed. Overall, the median OS was 15.9 month for eribulin compared to 14.5 months with capecitabine (HR = 0.879; 

 = 0.056). The PFS for eribulin compared to capecitabine was respectively 4.1 compared to 4.2 months (HR = 1.079; 

In subset analyses, patients with HER2-negative and triple-negative breast cancer seemed to benefit from treatment with eribulin, Gradishar points out. In HER2-negative patients the OS was 15.9 months for eribulin compared to 13.5 months for capecitabine (HR = 0.838; 

Gradishar believes these results indicate that eribulin is equal to capecitabine. This is meaningful, since eribulin is often used as a salvage therapy while capecitabine is commonly administered in earlier lines of treatment for metastatic breast cancer.

William J. Gradishar, MD, from the Northwestern University Feinberg School of Medicine, describes results from the 301 Study that compared eribulin mesylate to capecitabine for locally advanced or metastatic breast cancer.

Dr. William Gradishar Reviews the Eribulin 301 Study

William J. Gradishar, MD, Director, Maggie Daley Center for Women's Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, reviews results from the phase III LEA trial that investigated add-on bevacizumab (Avastin) in breast cancer.

The LEA trial examined the addition of bevacizumab to endocrine therapy as a first-line treatment for postmenopausal women with HER2-negative, hormone receptor-positive, advanced breast cancer. The endocrine therapies that were used in the trial were either letrozole or fulvestrant. In total, the trial enrolled 380 patients and evenly randomized them to receive endocrine therapy alone or in combination with bevacizumab.

This trial was unique in that it was the first to combine an antiangiogenic agent with endocrine therapy. Unfortunately, Gradishar notes, the trial did not demonstrate any additional value for adding bevacizumab in this setting.

Gradishar adds that at this point there is not a clear indication of which patients with breast cancer may benefit from bevacizumab.

William J. Gradishar, MD, from the Northwestern University Feinberg School of Medicine, reviews results from the phase III LEA trial that investigated add-on bevacizumab in breast cancer. 


Dr. Gradishar Reviews Findings From the LEA Trial

William J. Gradishar, MD, Director, Maggie Daley Center for Women's Cancer Care, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, discusses results from the international ATLAS study that was presented at the 2012 San Antonio Breast Cancer Symposium.

ATLAS enrolled 6846 women with estrogen receptor-positive breast cancer who had received 5 years of prior adjuvant tamoxifen. In the trial, patients were randomized to receive no tamoxifen or an additional 5 years of treatment. Overall, those who received 10 years of tamoxifen experienced a 25% lower recurrence rate and 29% lower mortality rates. The risk of dying due to breast cancer was also lower for those receiving an additional 5 years of treatment.

Gradishar notes that a benefit for the additional treatment was not evident in years 5 to 9. The greatest benefit was observed after 10 years of treatment. Due to the current standard of care, this information may have the greatest impact for premenopausal women who are not candidates for aromatase inhibitors, Gradishar points out.

William J. Gradishar, MD, from the Northwestern University Feinberg School of Medicine, discusses results from the international ATLAS study that was presented at the 2012 San Antonio Breast Cancer Symposium.

William J. Gradishar, MD

Articles

Dr. Gradishar on Endocrine Therapy in Early Stage Disease

Dr. Gradishar on Enriching Targeted Therapy Trials

Dr. William Gradishar Reviews the Eribulin 301 Study

Dr. Gradishar Reviews Findings From the LEA Trial

Dr. Gradishar Discusses 10 Years of Adjuvant Tamoxifen