Breaking News from ASH and SABCS

CURE, Winter 2007, Volume 6, Issue 6

News updates from the American Society of Hematology and the San Antonio Breast Cancer Symposium.

The annual meetings of the American Society of Hematology and the San Antonio Breast Cancer Symposium were held in December. Each gathering brought together thousands of cancer researchers, physicians, and others to report on critical issues in blood cancers and breast cancer, respectively. Details can be found at www.hematology.org and www.sabcs.org.

The VISTA study, a 682-patient phase III trial, found that adding Velcade (bortezomib) to melphalan/prednisone improved complete remission rates and overall survival in previously untreated multiple myeloma patients who were ineligible for stem cell transplantation. Nearly a third of patients in the Velcade arm achieved complete remission compared with 4 percent for patients receiving only melphalan/prednisone. Time to disease progression for Velcade patients was 24 months compared with 17 months for the melphalan/prednisone group.

Because multiple myeloma is predominantly diagnosed in older patients, most are unable to receive high-dose chemotherapy/stem cell transplant—the greatest chance of cure. The Velcade combination may be an alternative to transplant for these patients, say researchers.

Two new research studies have shown improved survival and disease-free survival for patients with mantle cell lymphoma, an incurable form of non-Hodgkin’s lymphoma that has around a 20 percent five-year survival rate. A phase II study tested a combination of immunochemotherapy and stem cell transplantation in 160 newly diagnosed patients, most with stage 4 disease.

Patients received Rituxan (rituximab) with standard CHOP (cyclophosphamide/doxorubicin/ vincristine/prednisone), which was alternated with high-dose Ara-C (cytarabine) and Rituxan. Fifty-five percent of patients had a complete response (disappearance of all visible tumor), and 41 percent had a partial response (tumor shrinkage of at least 30 percent). These patients then underwent chemotherapy and stem cell transplantation. Of the 91 percent of patients who completed the regimen, 72 percent had no disease progression after five years. Investigators hinted the new data may be the first step in finding a cure for mantle cell lymphoma.

A separate phase III study showed a combination of Treanda (bendamustine) and Rituxan had similar efficacy to CHOP/Rituxan, but with fewer side effects, including hair loss and infectious complications. Overall response was similar in both arms—94 percent compared with 93 percent, respectively. Longer follow-up data are still needed to know the relapse rate over time.

Revlimid (lenalidomide) with a high dose of the steroid Decadron (dexamethasone) is a standard treatment for multiple myeloma. But researchers say new data may result in a new standard of care. A phase III study has shown that a more tolerable regimen of Revlimid with low-dose Decadron resulted in fewer side effects and better survival rates. The two-year survival rate was 75 percent with high-dose Decadron compared with 87 percent in the group who received a low dose of the steroid. Side effects were more frequent in the high-dose arm, including deep vein thrombosis (25 percent compared with 9 percent) and infection.

Zevalin (ibritumomab tiuxetan), a monoclonal antibody that delivers radiation directly to cancer cells while sparing healthy tissue, was the focus of a phase III international trial in 414 advanced follicular non-Hodgkin’s lymphoma patients. Although follicular NHL is particularly responsive to radiation therapy, patients continually relapse and subsequently carry a worse prognosis.

Patients in partial or complete remission after chemotherapy were randomized to either observation or Zevalin. At about 18 months, researchers saw a significant advantage in progression-free survival for patients receiving Zevalin—37 months compared with 13 months in the observation group. This increase of two years resulted from only one injection of the drug with no further treatment. Side effects of Zevalin included a greater risk of infection. Nearly 80 percent of patients in partial remission after chemotherapy developed complete remission after Zevalin, regardless of prior therapy.

Studies described at the San Antonio Breast Cancer Symposium provide strong support for early-stage breast cancer treatments that do not rely on anthracycline drugs, with Adriamycin (doxorubicin) among the most common. The greatest concern is that, in some patients, anthracyclines appear to leave lasting damage to the heart.

As far back as 2003, data began to hint that an alternative non-anthracycline regimen, using Taxotere (docetaxel) and Cytoxan (cyclophosphamide), might offer as good or better disease-free survival for early-stage breast cancer.

The favorable trend toward a non-anthracycline alternative has continued in 2007. Researchers repor ted that seven years after treatment, women who received the non-anthracyline treatment have a better survival rate in general, as well as survival without cancer recurrence, something that has not been found in previous studies. At the end of the analysis, 87 percent of women who took the non-anthracycline regimen were alive, compared with 82 percent of those receiving the standard treatment.

A larger, randomized comparison is currently under way that will further compare the two types of drugs. For now, the decision to use anthracycline drugs will come down to each woman and her doctor, weighing the risk of recurrence against the risk of heart damage and other concerns.

—Laura Beil

AMERICAN SOCIETY OF HEMATOLOGY

SAN ANTONIO BREAST CANCER SYMPOSIUM

After a 12-year study, Canadian researchers have not discovered any difference between women who received hypofractionated radiation and those treated on a standard schedule. Hypofractionated radiation uses larger doses of radiation on a shorter schedule, sparing women weeks of radiation treatments.

At least four randomized trials have not found major differences in either the effectiveness or side effects between the two approaches. The latest study, presented in San Antonio, found results were practically identical in the risk of recurrence, breast appearance, and survival. Risk of recurrence was about 6 percent in both groups, and survival was 84 percent. The study involved more than 1,000 women whose cancer had not moved into the lymph nodes.

—Laura Beil

Another piece of the puzzle was revealed on the use of Oncotype DX, a high-tech gene test, to provide more precise estimates on risk of recurrence and which breast cancer patients will benefit the most from chemotherapy. The study presented included women with positive lymph nodes (Oncotype DX has only been used for node-negative cases) and looked at a more contemporary chemotherapy regimen containing Adriamycin.

Ten years after treatment, women with low gene test scores were shown not to benefit from chemotherapy. Disease-free survival was 60 percent for women treated with tamoxifen alone compared with 64 percent for women who received chemotherapy plus tamoxifen. Those with high scores, however, had significant improvement in disease-free and overall survival. Diseasefree survival after 10 years was 43 percent in the tamoxifen-alone group compared with 55 percent for women treated with chemotherapy plus tamoxifen. —Debu Tripathy, MD

New data show Zometa (zoledronic acid), a type of bisphosphonate, appears to increase bone mineral density among women receiving aromatase inhibitors, and the benefit lasts for at least three years.

Scientists have known aromatase inhibitors, which block estrogen production in postmenopausal women, can accelerate bone loss and raise the risk of fracture. Doctors are now testing whether drugs that treat osteoporosis might offset the bone-thinning tendencies of cancer treatment.

At SABCS, researchers reported that the benefit of Zometa held up for three years in 602 women with early-stage breast cancer enrolled in the Zometa-Femara Adjuvant Synergy Trial (Z-FAST). Half of the women received infusions of Zometa two times a year from the beginning of their treatment. The other half had their bone density monitored, and received the drug only if the density fell below a certain level.

After 36 months, the women who received Zometa upfront had experienced a 3.72 percent increase in spine density. The women who received no or delayed treatment had a 2.95 percent decrease in bone density. Experts are now developing recommendations for use of the drug.

—Laura Beil