Highlights from the 2005 American Society of Hematology
Meeting & the San Antonio Breast Cancer Symposium

Compiled From Staff Reports

American Society of Hematology Meeting

Treating Gleevec-Resistant CML

Among newly diagnosed chronic myelogenous leukemia (CML) patients who receive Gleevec® (imatinib), approximately 10 percent develop resistance to the drug after an initial response (see CURE, Summer 2005). In addition, most CML patients in advanced or blast phases of the disease do not have a long-lasting response to Gleevec, indicating a need for newer agents. Dasatinib (BMS-354825) is an effective oral drug against Gleevec-resistant CML. Preliminary analyses of several phase II trials reported at the American Society of Hematology meeting in December showed as many as 66 percent of Gleevec-resistant CML patients responded to dasatinib. Side effects included low white blood cell count, diarrhea and nausea. AMN107 is another investigational agent that treats patients with chronic phase and advanced-stage Gleevec-resistant CML. A phase I trial of more than 100 patients taking AMN107 showed that among 34 CML patients with a bcr-abl mutation before treatment, 14 achieved a cytogenetic response, meaning no cells contained the Philadelphia chromosome (a genetic mutation that produces the bcr-abl protein). Most side effects were minor and included constipation, nausea, vomiting and fatigue. Although not definitive, these encouraging results have led to the initiation of phase II testing.
— Chris Schwab, PhD

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San Antonio Breast Cancer Symposium

Advances in Early-Stage Breast Cancer

Herceptin® (trastuzumab) is an antibody that targets the HER2 protein and improves survival of patients with HER2-overexpressing metastatic breast cancer. Now, patients with earlier stages of breast cancer can also benefit from the drug. In early 2005, results from three major studies showed that HER2-positive patients given Herceptin after surgery had a lower chance of recurrence. At the San Antonio Breast Cancer Symposium in December, updated results from the international HERA trial demonstrated a 46 percent reduction in disease recurrence in patients treated with one year of Herceptin following surgery and conventional chemotherapy, and a 24 percent improvement in overall survival. A second trial compared three treatment regimens, two of which contained Herceptin and one that did not. Both Herceptin-containing regimens produced significant reductions in the risk of recurrence. Further studies are necessary to determine the optimal duration of Herceptin therapy.
— Susan Peck, PhD

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Avastin Improves Efficacy of Chemotherapy

Avastin® (bevacizumab), a monoclonal antibody that stops blood vessel growth in tumors, can improve the effectiveness of Taxol® (paclitaxel) in women with advanced breast cancer. Updated results of a study reported that of 680 women with advanced breast cancer, adding Avastin to Taxol doubled the response rate—from 14 percent to almost 30 percent. The cancer stayed under control almost five months longer in women who received Avastin with Taxol compared with Taxol alone. Genentech, the maker of Avastin, plans to file for approval in patients with advanced breast cancer.
— Chris Schwab, PhD

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Predicting Outcome in Breast Cancer

Gene expression profiling can determine the presence or absence of thousands of genes or proteins in a patient’s cancer cells. Oncotype DX™ is one such test that analyzes 21 different genes—the presence or absence of which determines a “recurrence score.” Previous analyses have shown that the higher the recurrence score, the more likely a patient will develop distant metastases within 10 years. Trial data demonstrated a similar association between a patient’s recurrence score and local or regional disease recurrence. Likewise, microarrays have been used to identify a 76-gene signature to subclassify tumors. The gene profile was highly useful in identifying patients who developed distant metastases within five years, regardless of whether they received tamoxifen.
— Tara Beers Gibson, PhD

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Marker for Survival

As a tumor grows, individual cells sometimes break away and travel through the bloodstream to other parts of the body. New techniques, including a
commercially available method called CellSearchTM, allow doctors to measure the presence of circulating tumor cells (CTCs) in the blood, which can predict survival in patients with metastatic breast cancer (see CURE, Summer 2005). For breast cancer, the cutoff appears to be five CTCs per 7.5 mL of blood. A clinical trial reported progression-free survival was 18 months for patients who received chemotherapy alone and had fewer than five CTCs compared with seven months for patients with five or more CTCs. Measurement of CTCs may be a useful method to predict benefit from chemotherapy and hormonal therapy and may allow physicians to switch to an alternative treatment if the CTC count remains high after initial therapy.
— Tara Beers Gibson, PhD