Pharmacy & Therapeutics - March 2008 - (Page 148) Meeting Highlights San Antonio Breast Cancer Symposium Walter Alexander This year’s conference at the Henry B. Gonzalez Convention Center in San Antonio, Texas, attracted a record number of researchers, exhibitors, and general attendees (8,600) from 83 nations to a varied slate of sessions on the latest research and epidemiological trials in breast cancer. Some key presentations on short courses of chemotherapy, aromatase inhibitors, cancer recurrence, and treatment-resistant disease are reviewed. Short-Course Therapy with Xeloda, Taxotere, and Herceptin Presenter: Debu R. Tripathy, MD, Professor of Internal Medicine, University of Texas, San Antonio, Tex. When investigators at Texas Southwestern Medical Center in San Antonio postulated that the known synergy and good tolerability of three drugs would bring favorable results in patients with early breast cancer, they found that a short course of therapy was beneficial. The combination, which included two chemotherapy agents—capecitabine (Xeloda, Roche) plus docetaxel (Taxotere, Sanofi-Aventis) with the addition of trastuzumab (Herceptin, Genentech)—among women with HER-2–positive (HER-2+) status produced clinical responses in about 75% of those enrolled. (HER is defined as human epidermal growth factor receptor.) The clinical trial, conducted by Dr. Tripathy, included 156 women (median age, 52 years) with newly diagnosed tumors confined to the breast or to axillary nodes without distant spread; 122 were HER-2–negative (HER-2–), and 34 were HER-2+. They received open-label, oral Xeloda given at a dose of 825 mg/m2 twice daily on days 1 to 14 every three weeks and intravenous (IV) Taxotere at a dose of 75 mg/m2 on day 1 every three weeks. IV Herceptin was given to the HER-2+ patients at a 4-mg/kg loading dose, then 2 mg/kg on days 1, 8, and 15 every three weeks. The primary endpoint was the rate of combined pathological complete response (pCR) and near pathological complete response (npCR) of residual tumor up to T1a status in the affected breast after four cycles of Xeloda and Herceptin. The primary endpoint was reached in 15% of HER-2– women and in 50% of HER-2+ women. Although overall clinical response rates were similar for HER-2– patients (76%) and HER-2+ patients (73%), complete responses were nearly doubled in the HER-2+ arm (22% and 42%, respectively). In the HER-2– and the HER-2+ arms, mean tumor size decreased from 5.6 cm and 6.1 cm at baseline to 1.6 cm and 2.8 cm after four cycles. In the 33 highly treatment-resistant “triple-negative” patients (with HER-2–, estrogen receptor– negative [ER–], and progesterone receptor–negative [PR–] status), the rate of pCR plus the npCR rate was 36.4%. Among women with ER–/PR–/HER-2+ status, the rate was 66.7%. Dr. Tripathy noted that typical rates for pCR plus npCR after four cycles of chemotherapy ranged from 10% to 15%. Very few The author is a freelance medical writer living in New York, New York. patients had to stop therapy because of toxicity. He concluded: “These results suggest that a short course of Xeloda plus Taxotere is a reasonably active, non–anthracycline-containing preoperative treatment option.” The findings, he said, justify larger trials comparing combination and standard chemotherapy regimens. Aromatase Inhibitors and Bone Loss Presenter: Adam Brufsky, MD, PhD, University of Pittsburgh, Pittsburgh, Pa. The use of aromatase inhibitors can increase disease-free survival in postmenopausal women with estrogen receptor– positive (ER+) or progesterone receptor–positive (PR+) breast cancer, but it also brings about nearly complete ablation of estrogen production, leading to accelerated bone loss and an increased risk of fractures. Although oral bisphosphonates have proven efficacy in postmenopausal osteoporosis, they are often poorly tolerated. “Compliance can be an issue,” stated Dr. Brufsky. Dr. Brufsky presented long-term results of the Zometa– Femara Adjuvant Synergy Trial (Z-FAST). This trial evaluated the efficacy and safety of zoledronic acid (Zometa, Novartis) in preventing bone loss associated with aromatase inhibitors in postmenopausal women with early breast cancer who were receiving adjuvant therapy with letrozole (Femara, Novartis). It also compared initial (“up-front”) therapy with treatment that was delayed until either post-baseline T-scores decreased to –2 or below or until a clinical fracture occurred. A T-score of 1.0 is normal, –1.0 represents mild bone thinning, and –2.5 is considered to be osteoporosis. The trial included 600 postmenopausal women (median age, 60 years) with stage I to III ER+ and/or PR+ breast cancer who were receiving Femara 2.5 mg once daily for five years. The patients were randomly assigned to receive up-front therapy or delayed IV Zometa 4 mg every six months as well as calcium and vitamin D. The primary endpoint was the percentage of change in lumbar spine bone mineral density. Most women (about 85%) had T-scores between –1 and –2 at the baseline evaluation. Dr. Brufsky reported changes in bone density after 36 months of treatment in 274 women; 140 women received initial therapy, and 133 received delayed treatment. Lumbar spine bone density increased by a mean of 4% in the patients receiving initial Zometa therapy but dropped by almost 3% in the delayed Zometa group, for a 7% difference (P < 0.001). Similarly, differences in total bone density of the hip favored 148 P&T® • March 2008 • Vol. 33 No. 3
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