Purpose: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. Patients and Methods: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m2) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. Results: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. Conclusion: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non‐cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up. J Clin Oncol 17:3412-3417. r 1999 by American Society of Clinical Oncology.
PURPOSE: To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2–overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels. PATIENTS AND METHODS: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m 2 /wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle. RESULTS: The median delivered dose-intensity of docetaxel was 24 mg/m 2 /wk (range, 18 to 27 mg/m 2 /wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 44% to 80%). The ORR in patients whose tumors were HER-2–positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P = .04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing. CONCLUSION: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2–overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.
<p>Survival outcomes. <b>A,</b> Kaplan–Meier plot of EFS for all patients. <b>B,</b> Kaplan–Meier plot of EFS separated by pathological response. <b>C,</b> Kaplan–Meier plot of MFS for all patients. <b>D,</b> Kaplan–Meier plot of MFS separated by pathological response. <b>E,</b> Kaplan–Meier plot of OS for all patients. <b>F,</b> Kaplan–Meier plot of OS separated by pathological response.</p>
527 Background: Trastuzumab (T) was approved for the adjuvant treatment of women with early-stage, HER-2 overexpressing (HER2+) breast cancer in 2006. There are limited data outlining the outcomes of patients with HER2+ breast cancer who receive adjuvant T-based therapy and then receive T and/or lapatinib in the metastatic setting. Methods: We identified 540 patients with HER2+ breast cancer treated with T or lapatinib as part of their first-line treatment for metastatic disease from 01/1997 to 11/2011. HER-2 positivity was assessed by immunohistochemistry (score, 3+) or fluorescence in situ hybridization (HER2/CEP17 ratio ≥ 2). We excluded 17 patients from this analysis because they were either lost to follow-up or received less than 2 cycles of therapy at the institution. Statistical analyses were performed using the chi-square test to compare proportions between groups and the Cox proportional hazards regression analysis to compare survival times and estimate the corresponding hazard ratio with 95% confidence interval. Results: Of the 523 patients eligible for analysis, 76 patients had received T in the adjuvant setting and 447 had not. In the group who did not receive adjuvant T, 48% (213/447) of patients achieved a complete or partial response (CR/PR), whereas only 13% (14/76) achieved a CR/PR in the adjuvant T group (P<.0001). After adjustment for age, disease-free interval, post-menopausal status, stage at presentation, ER/PR status, and nuclear grade, the odds ratio was 0.27 (CI 0.13 - 0.56, p = 0.0004). Overall survival from first evidence of metastasis was significantly longer in the group who did not receive adjuvant T (39 months vs. 24 months, HR = 1.8, 95% CI 1.3-2.4). For OS, the adjusted hazard ratio was 1.5 (CI 1.04 - 2.1, p = 0.029). Age, DFI and stage were also significant predictors of OS. Conclusions: Patients with HER2+ metastatic breast cancer who were T naive, had a higher response rate (CR/PR) to front line HER2 targeted therapy and a longer OS compared to patients with metastatic HER2+ breast cancer who received T in the adjuvant setting. These findings highlight the importance of recognizing a pre-treated population and calls for further research in this area.
PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m 2 ) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non–cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.
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