Pharmacy & Therapeutics- July 2008

MEETING HIGHLIGHTS American Society of Clinical Oncology Walter Alexander The 2008 American Society of Clinical Oncology Meeting, the 44th and the largest so far in its history, hosted 34,000 oncologists and industry exhibitors, with 312 journalists on-site. Among more than 11,000 abstracts presented, key sessions touched on the pharmacological treatment of breast cancer, renal cell carcinoma, chronic myelogenous leukemia, non–small-cell lung cancer, bone resorption, and advanced melanoma. Endocrine Therapy plus Zoledronic Acid (Zometa) And Breast Cancer Recurrence • Michael Gnant, MD, Medical University of Vienna, Vienna, Austria In what was surely one of the most striking findings of the entire conference, zoledronic acid (Zometa, Novartis) 4 mg, given every six months, significantly improved clinical outcomes among women with endocrine-responsive early breast cancer in the Austrian Breast Cancer Study Group-12 (ABCSG) Trial. The implication, stated Dr. Gnant, “is that a low- and intermediate-risk patient subgroup can be spared the side effects of cytotoxic therapy after locoregional treatment.” The trial’s intent was to determine whether treatment with surgery plus goserelin acetate (Zoladex, AstraZeneca) could prevent recurrence in premenopausal women with early-stage breast cancer. The researchers randomly assigned 1,803 women (median age, 45 years) to receive either tamoxifen (Nolvadex) or anastrozole (Arimidex), both made by AstraZeneca, to compare the two endocrine suppressive agents. After the patients underwent surgery and radiation, they received goserelin 3.6 mg every 28 days; they were then randomly assigned to receive tamoxifen 20 mg/day or anastrozole 1 mg/day. The primary endpoint was disease-free survival. After a median follow-up of 60 months, Dr. Gnant said, no treatment differences were found with either drug in this component of the trial. Disease-free survival of at least five years was reported for 94% of women, and five-year overall survival was observed for 98.2%. Differences did appear, however, in a sub-randomization study in which half of each treatment group also received zoledronic acid. For the women receiving zoledronic acid 4 mg every six months, about 94% achieved five-year progressionfree survival, compared with 91% of patients not receiving the bisphosphonate. The 3% absolute difference translated to a relative risk reduction of about 35% (P = 0.011 level). Recurrencefree survival was also significantly improved in the zoledronic acid group, with a hazard ratio (HR) of 0.653 (35% reduction, P = 0.014). The zoledronic acid patients showed a favorable trend in overall survival (HR = 0.595, P = 0.10), with 16 deaths, compared with 26 deaths in the group not given zoledronic acid. Other reductions in contralateral breast cancer and in distant non-bone metastases were reported with zoledronic acid. The combination of adjuvant endocrine therapy and zol- edronic acid therapy was well tolerated, without incidence of osteonecrosis of the jaw or renal toxicity, Dr. Gnant said. He concluded, “Zoledronic acid significantly improves clinical outcomes beyond those achieved with endocrine therapy alone.” Everolimus (RAD001) in Renal Cell Carcinoma • Robert Motzer, MD, Memorial Sloan-Kettering Cancer Center, New York, N.Y. • Brian I. Rini, MD, Glickman Urologic and Kidney Institute, Cleveland, Ohio Everolimus, an investigational therapy, prolonged progression-free survival in renal cell carcinoma (RCC) patients whose disease had progressed while they were receiving vascular endothelial growth factor receptor (VEGF-R)/tyrosine kinase inhibitor (TKI) therapy with sunitinib (Sutent, Pfizer), sorafenib (Nexavar, Bayer), or both. Everolimus targets mTOR (mammalian target of rapamycin) protein, a central regulator of tumor cell division, cell metabolism, and angiogenesis. The phase 3 clinical trial finding was reported by Dr. Motzer. The trial included 410 patients falling within Sloan-Kettering’s risk-stratification groups of “favorable,” intermediate,” or “poor,” who were randomly assigned to receive oral everolimus 10 mg/day plus best supportive care (n = 272) or placebo plus best supportive care (n = 138). Median age was 60 years. In both groups, 94% of patients had two or more metastatic sites. Each patient had previously been treated with other agents: 71% with sunitinib, 55% with sorafenib, and 26% with both. The primary endpoint was progression-free survival. After the second interim analysis, the Independent Monitoring Committee recommended termination of the study’s placebo arm; these patients were offered treatment with everolimus. Median progression-free survival was four months for the everolimus patients and 1.9 months in the placebo group (HR = 0.30, P < 0.001). Progression-free survival was 4.8 months for everolimus and 1.8 months for placebo; at six months, the progression-free survival rate was 26% for the everolimus patients and 2% for the placebo patients. The benefits of this agent were reported for all subgroups according to their risk; the TKI agent used; and the patient’s age, sex, and geographic region. Median overall survival, which had not been reached in the everolimus group, was 8.8 months with placebo (HR = 0.83, P = 0.23). Everolimus was generally well tolerated; 10% of patients discontinued treatment because of adverse events, compared with 4% who withdrew in the placebo group. Stomatitis was the most common event (in 36%), but grade 3 and 4 events were The author is a medical writer living in New York, New York. 398 P&T® • July 2008 • Vol. 33 No. 7

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics- July 2008

Pharmacy & Therapeutics- July 2008 Contents Editorial Medication Errors Prescription Washington New Drugs/Drug News/New Medical Devices Drug Forecast FDA's Janet Woodcock Riding High American Society of Clinical Oncology The Pharmacological Management of Migraine, Part I CE Test and Forms The Law of Unintended Consequences

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.