Pharmacy & Therapeutics - September 2008 - (Page 525)

DRUG FORECAST 8.2 months (95% CI, 5.7–10.2 months). In addition, 35% of patients achieved stable disease. Median overall survival was 22 months (95% CI, 15.6–27 months).39 The highest response rate was noted in a single-arm, phase 2 study in which ixabepilone (6 mg/m2 infused over one hour on five consecutive days ever y three weeks) was given as a first-line or a subsequent therapy to 23 patients with metastatic breast cancer.40 These patients were taxane-naive, but 70% had received anthracycline and/or capecitabine earlier. 40 In total, 13 patients (57%) had partial responses and six patients (26%) had stable disease, resulting in an ORR of 57% (95% CI, 34.5%– 76.8%) with a median duration of 5.6 months. Median time to disease progression was 5.5 months.40 In these phase 2 studies, lower response rates were observed with tumors that were refractory to taxane; however, given the highly unresponsive nature of this type of disease, the response to ixabepilone remains clinically relevant. An additional phase 2 trial was conducted in patients with metastatic breast cancer who had experienced disease progression while receiving, or within four months of receiving, a taxane (or within six months if they had received adjuvant taxane therapy) and who had been given a taxane as their most recent regimen.37 In total, 49 patients received ixabepilone as a three-hour infusion of 40 mg/m2 ever y three weeks, resulting in a response rate of 12% (95% CI, 4.7%–26.5%). All six responses were partial, and five of these occurred in patients who had not responded to prior taxane therapy. The median response duration was 10.4 months. In addition, 20 patients achieved stable disease. The median time to progression was 2.2 months (95% CI, 1.4–3.2 months), and median survival was 7.9 months.37 In another phase 2 study, 37 patients with breast cancer with measurable disease who had received paclitaxel, docetaxel (Taxotere, Sanofi-Aventis), or both, as prior neoadjuvant, adjuvant, or metastatic therapy received IV ixabepilone at 6 mg/m2 per day on days one through five every three weeks.38 The best responses included a complete response in one patient (3%), par tial responses in seven patients (19%), and stable disease in 13 patients (35%). A small phase 2 study evaluated ixabepilone (8–10 mg/m2 per day for three days every three weeks) in patients with metastatic breast cancer who had previously received taxanes.42 In this trial, at least one response among the first 12 patients was required for accrual to continue to a total of 37 patients. No complete or partial responses were observed (N = 12). The authors concluded that these dosages of ixabepilone were not effective in this heavily pretreated population. This outcome might have resulted from the fact that the patient population had not achieved adequate dose density. In the phase 2 registration trial,36 ixabepilone was administered as a 40-mg/ m2 IV infusion given over three hours every three weeks in a multicenter, single-arm study of patients with metastatic breast cancer that was resistant to earlier therapy with anthracyclines, taxanes, and capecitabine. The primary endpoint was the ORR. Secondary endpoints included time to response, response duration, progression-free survival, and tolerability. In this study, patients were heavily pretreated and had disease resistance to multiple earlier therapies. Of 126 enrolled patients, 88% had received two or more previous antineoplastic regimens in the metastatic setting, 64% had three or more metastatic sites, 77% had visceral disease, and 33% had triple-negative tumors. Triple-negative tumors are common in premenopausal women, and they are aggressive and resistant to standard antineoplastic agents used to treat metastatic breast cancer. An ORR was achieved in 11.5% (95% CI, 6.3%–18.9%) of patients, as assessed by an independent Table 1 Response Rates in Clinical Trials of Ixabepilone Monotherapy in Metastatic Breast Cancer: Key Phase 2 Trials Trial Baselga et al. Denduluri et al.40 Roché et al.39 Low et al.38 41 Eligibility Criteria Neoadjuvant therapy in patients with locally advanced breast cancer 1st- or >2nd-line therapy in patients with taxanenaive MBC 1st-line therapy in patients with MBC previously treated with an adjuvant anthracycline 1st- 2nd-, or >3rd-line therapy in patients previously treated with a taxane as prior neoadjuvant, adjuvant, or metastatic therapy 1st-, 2nd-, 3rd-, or 4th-line therapy in patients with taxane-resistant MBC 3rd- or 4th-line therapy in patients with MBC resistant to anthracyclines, taxanes, and capecitabine Patients with MBC who have received prior taxane therapy No. 164 23 65 37 Dose and Schedule 40 mg/m q3w 6 mg/m2 days 1–5 q3w 40 mg/m2 q3w 6 mg/m2 days 1–5 q3w 40 mg/m2 q3w 40 mg/m2 q3w 8–10 mg/m2 q3w 2 Response Rate pCR rate, 19% ORR, 57%; SD rate, 26% ORR, 41.5%; SD rate, 35% ORR, 22%; SD rate, 35% ORR, 12%; SD rate, 41% ORR, 11.5%; SD rate, 50% ORR, 0%; SD rate for ≥6 weeks, 83% Thomas et al.37 Perez et al.36 Denduluri et al.42 49 126 12 MBC = metastatic breast cancer; ORR = objective response rate; q3w = every 3 weeks; pCR = pathological complete response; SD = stable disease. Vol. 33 No. 9 • September 2008 • P&T® 525

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

Pharmacy & Therapeutics - September 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Effect of Prescription Copays on Adherence and Treatment Failure with Oral Antidiabetic Medications Vaccine Declinations Present New Challenges for Public Health Universal Health Care in America Digestive Disease Week and American Diabetes Association Pharmaceutical Approval Update

Pharmacy & Therapeutics - September 2008

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.