Herceptin plus Epirubicin and Cyclophosphamide Tolerable and Effective for HER2-positive Metastatic Breast Cancer

For women with metastatic, HER2-positive breast cancer, the combination of HerceptinR (trastuzumab) with epirubicin and cyclophosphamide appears to offer a promising treatment option with a relatively low rate of heart complications. These results were published in the Journal of Clinical Oncology.

Twenty to 25 percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-positive breast cancer.

Herceptin may be used in addition to chemotherapy. Anthracycline-based chemotherapy regimens are effective against breast cancer but can increase the risk of heart problems when combined with Herceptin.

Epirubicin is an anthracycline that may produce fewer heart problems than some other commonly used anthracyclines. To evaluate the combination of Herceptin with epirubicin and cyclophosphamide, researchers in Europe conducted a Phase I/II clinical trial known as HERCULES. The study enrolled 120 women with HER2-positive, metastatic breast cancer and adequate heart function. These women were treated with Herceptin, one of two doses of epirubicin (60 mg/m2 or 90 mg/m2), and cyclophosphamide. Herceptin was then given alone until cancer progression.

Outcomes in the women with HER2-positive breast cancer were compared with outcomes among 60 women with metastatic, HER2-negative breast cancer. The women with HER2-negative breast cancer were treated with the higher dose of epirubicin and cyclophosphamide alone (without Herceptin).

Among women treated with Herceptin plus chemotherapy, dose-limiting heart problems occurred in 5% of women given the higher dose of epirubicin and 1.7% of women given the lower dose of epirubicin. These heart problems were described as “manageable,” and no heart-related deaths occurred. None of the women with HER2-negative cancer (who were treated with chemotherapy without Herceptin) developed dose-limiting heart problems.Tumor response rates were 57% among women treated with Herceptin and the lower dose of epirubicin and 60% among women treated with Herceptin and the higher dose of epirubicin.

The researchers conclude that the combination of Herceptin, epirubicin, and cyclophosphamide is a promising approach for the treatment of HER2-positive metastatic breast cancer and warrants additional research.

Reference: Untch M, Muscholl M, Tjulandin S et al. First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial. Journal of Clinical Oncology. 2010; 28:1473-1480.

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Herceptin Given At Same Time As Chemotherapy May Provide Most Benefit for Breast Cancer

The results of a Phase III clinical trial suggest that starting HerceptinR (trastuzumab) during chemotherapy for early-stage, HER2-positive breast cancer may be more effective than starting Herceptin after chemotherapy has been completed. These results were published in the Journal of Clinical Oncology.????

Fifteen to 20 percent of?breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-targeted breast cancer.????

The optimal timing of Herceptin was evaluated in a Phase III clinical trial known as NCCTG N9831. The study enrolled women with Stage I-III HER2-positive breast cancer.? All women received chemotherapy with doxorubicin and cylophosphamide followed by paclitaxel, and some women also received Herceptin. Herceptin was started either at the same time as paclitaxel or later (after chemotherapy had been completed), and was given for a total of 52 weeks.????

Women who received both Herceptin and chemotherapy had a lower risk of cancer recurrence than women who received chemotherapy alone.?Women who started Herceptin at the same time as paclitaxel appeared to derive the most benefit. Five-year disease-free survival was 84.4% among women who received concurrent Herceptin and paclitaxel, compared with 80.1% among women who started Herceptin after finishing treatment with paclitaxel. This result did not meet the criteria for statistical significance, however, suggesting that it could have occurred by chance alone.?Starting Herceptin at the same time as paclitaxel did not appear to substantially increase the risk of side effects compared with starting Herceptin after chemotherapy had been completed.?

For women with early-stage, HER2-positive breast cancer, these results suggest that starting Herceptin during chemotherapy may produce better results than starting Herceptin after chemotherapy has been completed.?

Reference:?Perez EA, Suman VJ, Davidson NE et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. Journal of Clinical Oncology. 2011;29:4491-4497.?

Posted December 4, 2011

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Adding Afinitor to Herceptin May Provide Breast Cancer Benefit

For women with HER2-positive breast cancer that worsens in spite of treatment with HerceptinR (trastuzumab), treatment with a combination of Herceptin and AfinitorR (everolimus) may provide a benefit. These results were published in the Journal of Clinical Oncology.????

Approximately 20-25% of breast cancers overexpress (make too much of) the HER2 protein. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but researchers continue to explore new approaches to treatment. One important focus of research is the treatment of cancer that has progressed after prior HER2-targeted therapy.???

Afinitor is an oral medication that works by inhibiting a protein known as mTOR. The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth.?Currently, Afinitor is used for the treatment of selected patients with kidney cancer, pancreatic neuroendocrine tumors, and subependymal giant cell astrocytoma (SEGA).?

To evaluate the combination of Herceptin and Afinitor, researchers combined information from two clinical trials that were conducted concurrently. Information was available for 47 women with HER2-positive metastatic breast cancer that had progressed during treatment with Herceptin. Study participants received Herceptin every three weeks in combination with daily Afinitor.????

Seven patients (15%) had a partial response to treatment (a reduction in detectable cancer).?An additional nine patients (19%) experienced stable disease for six months or longer. ?Median duration of survival without cancer progression was 4.1 months.?Side effects included fatigue, infection, and mouth sores (mucositis).?

These results suggest that the combination of Afinitor and Herceptin may benefit women with HER2-positive, advanced breast cancer that has worsened in spite of Herceptin treatment. Afinitor has been approved by the US Food and Drug Administration for other purposes, but has not yet been approved for breast cancer. At this time, the use of Afinitor would only be appropriate for women with ?HER2-positive breast cancer in the setting of a clinical trial.? Additional, ongoing studies are evaluating the combination of Herceptin, Afinitor, and chemotherapy in the first- and second-line treatment of metastatic breast cancer. ?

Reference: Khanh Morrow P, Wulf GM, Ensor J et al. Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy. Journal of Clinical Oncology. Early online publication July 5, 2011.?

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Herceptin and Chemotherapy Benefit Breast Cancer Patients with Brain Metastases

Among women with HER2-positive breast cancer that has spread to the brain, treatment with HerceptinR (trastuzumab) and/or chemotherapy can prolong survival. These results were published in Clinical Cancer Research.???

Although important advances have been made in breast cancer treatment, the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body) remains challenging. The brain is one area to which breast cancer may spread, and researchers continue to explore how best to manage patients with brain metastases.?????

To assess the frequency and outcome of brain metastases in women with metastatic HER2-positive breast cancer, researchers conducted a study among 1,023 newly diagnosed patients. HER2-positive breast cancer refers to cancer that overexpresses (makes too much of) the HER2 protein. Treatment of HER2-positive breast cancer often includes a HER2-targeted therapy such as Herceptin.???

Brain metastases were more common in younger women, those with hormone receptor-negative breast cancer, and those with a greater amount of cancer.?Among women who were free of brain metastases at the time of their initial diagnosis but later developed brain metastases, brain metastases were diagnosed a median of 13 months after initial diagnosis.?After the diagnosis of brain metastases, treatment with Herceptin and chemotherapy each significantly improved overall survival.??

These results suggest that even after HER2-positive breast cancer spreads to the brain, standard breast cancer treatments can prolong survival.?

Reference: Brufsky AM, Mayer M, Rugo HS et al. Central nervous system metastases in patients with HER2-positive metastatic breast cancer: incidence, treatment, and survival in patients from registHER. Clinical Cancer Research. 2011; 17: 4834–43.?

Posted July 20, 2011

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