Review - Haymarket Media Group

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<strong>Review</strong> and to test for significant differences in the times to events. A post hoc analysis of outcomes according to hormone receptor status and HER2 status was performed. Study Results Between October 1999 and January 2002, 5052 patients were enrolled, of whom 4950 were eligible. The benefit of weekly paclitaxel was seen in patients with HER2-negative disease irrespective of their hormone receptor status. There were no significant differences among the patient groups. The median age was 51 years, and the majority of patients were hormone receptor positive (69.5%) and HER2 negative (67.5%). Most patients (97%) received all four cycles of doxorubicin and cyclophosphamide. The proportions of patients who received all taxane doses were 95% (paclitaxel Table 1 5-Year Disease-Free Survival and Overall Survival in Four Treatment Arms 12 The American Journal of Hematology/Oncology every 3 weeks), 88% (paclitaxel weekly), 87% (docetaxel every 3 weeks), and 75% (docetaxel weekly). The proportions of patients who required dose modification of the taxane were 22%, 29%, 28%, and 40%, respectively. At a median follow-up of 63.8 months, 1048 patients had a recurrence of breast cancer or cancer in the contralateral breast, and 686 had died. The estimated 5-year disease-free survival rates were 76.9% for the patients receiving every-3-week paclitaxel, 81.5% for patients receiving weekly paclitaxel, 81.2% for patients receiving every-3-week docetaxel, and 77.6% for patients receiving weekly docetaxel (Table 1). The study met its end point and demonstrated a significant improvement in disease-free survival in the group receiving weekly paclitaxel and in the group receiving docetaxel every 3 weeks (Table 2). Weekly paclitaxel compared with standard therapy was associated with an improved overall survival (hazard ratio, 1.32, P=0.01) that was not seen in the patients receiving weekly docetaxel or every-3-week docetaxel (Table 3). Recent data have suggested that patients with hormone receptor–positive and HER2-negative breast cancer may not derive a benefit from adjuvant taxane therapy. 7 Therefore, the investigators analyzed the effect of hormone receptor status and HER2 expression on the efficacy of weekly paclitaxel Treatment Arm 5-Year Disease-Free Survival 5-Year Overall Survival Every-3-week paclitaxel 76.9% 86.5% Weekly paclitaxel 81.5% 89.7% Every-3-week docetaxel 81.2% 87.3% Weekly docetaxel 77.6% 86.2% Table 2 Hazard Ratio for Disease-Free Survival in the Experimental Treatment Arms Compared With Standard Every-3-Week Paclitaxel Treatment Arm Hazard Ratio 95% CI P Value Weekly paclitaxel 1.27 1.03-1.57 0.006 Every-3-week docetaxel 1.23 1.00-1.52 0.02 Weekly docetaxel 1.09 0.89-1.34 0.29
and demonstrated that patients with HER2-negative disease had improved disease-free and overall survival with weekly paclitaxel irrespective of hormone receptor status (Table 4). Grade 3/4 toxic effects were more common in patients receiving the every-3-week docetaxel (71%) compared with those receiving weekly docetaxel (45%), weekly paclitaxel (28%), or every-3-week paclitaxel (30%). The majority of grade 3/4 adverse events in the every-3-week docetaxel arm was related to neutropenia (46%), infection (13%), and neuropathy (4%). Neuropathy of grade 2, 3, and 4 was more common in the weekly paclitaxel group compared with paclitaxel every 3 weeks (27% vs 20%). Other adverse effects were similar in the weekly and every-3-week paclitaxel groups. Discussion In women with lymph node–positive or high-risk lymph node–negative breast cancer, weekly paclitaxel compared with standard taxane therapy every 3 weeks resulted in a significantly improved overall and disease-free survival. Patients receiving docetaxel every 3 weeks also had improved disease-free sur- Weekly paclitaxel and breast cancer Table 3 Hazard Ratio for Overall Survival in the Experimental Treatment Arms Compared With Standard Every-3-Week Paclitaxel Treatment <strong>Group</strong> Hazard Ratio 95% CI P Value Weekly paclitaxel 1.32 1.02-1.72 0.01 Every-3-week docetaxel 1.13 0.88-1.46 0.25 Weekly docetaxel 1.02 0.80-1.32 0.80 Table 4 Disease-Free and Overall Survival in HER2-Negative Patients According to Hormone Receptor (HR) Status Variable Hazard Ratio 95% CI P Value Overall survival HR+ 1.36 0.92-2.00 0.12 HR– 1.33 0.91-1.94 0.14 Disease-free survival HR+ 1.31 1.00-1.72 0.05 HR– 1.37 0.98-1.93 0.97 vival but not overall survival. These results are consistent with findings in metastatic breast cancer that demonstrate a benefit of weekly paclitaxel or every- 3-week docetaxel compared with every-3-week paclitaxel. Treatment with doxorubicin and cyclophosphamide was well tolerated, with 97% of patients completing all four cycles. The majority of patients in all treatment arms also completed taxane therapy. Toxic effects, mainly neutropenia, infection, and grade 2, 3, or 4 neuropathy, were more common in the every-3-week docetaxel group compared with the other groups. Of particular interest was that the benefit of weekly paclitaxel was seen in patients with HER2negative disease irrespective of their hormone receptor status. This is contradictory to recent data from Hayes and colleagues, who suggested that the benefit of adjuvant taxane therapy was not seen in patients with hormone receptor–positive disease or HER2-negative disease. 8 The results from the recent ECOG trial are consistent with those demonstrated in a subgroup analysis of the GEICAM 9906 trial, which compared six cycles of fluorouracil, epirubi- November 2008 • Vol 7 • Supplement 5 13
Page 1 and 2: ajho.com November 2008 • Vol 7
Page 3 and 4: LettertoOurReaders Dear Colleague,
Page 5 and 6: hand-foot syndrome, 23.9% vs 31.1%;
Page 7: Figure Paclitaxel 175 mg/m2 every 2
Page 11 and 12: Commentary Optimizing Taxane Therap
Page 13 and 14: HER2 Status and Inflammatory Breast
Page 15 and 16: year OS was 53.1% (95% CI, 44.0%-61
Page 17 and 18: include those related to cell motil
Page 19 and 20: CaseStudy Risk of Local Recurrence
Page 21 and 22: factors such as age and margin stat

Review - Haymarket Media Group

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