scholarly journals Independent Review of E2100: A Phase III Trial of Bevacizumab Plus Paclitaxel Versus Paclitaxel in Women With Metastatic Breast Cancer

2009 ◽  
Vol 27 (30) ◽  
pp. 4966-4972 ◽  
Author(s):  
Robert Gray ◽  
Suman Bhattacharya ◽  
Christopher Bowden ◽  
Kathy Miller ◽  
Robert L. Comis
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Original Data ◽  
Phase Iii ◽  
Open Label ◽  
Phase Iii Trial ◽  
Independent Review

Purpose E2100, an open-label, randomized, phase III trial conducted by the Eastern Cooperative Oncology Group (ECOG), demonstrated a significant improvement in progression-free survival (PFS) and overall response rate (ORR) with paclitaxel plus bevacizumab compared with paclitaxel alone as initial chemotherapy for patients with HER2-negative metastatic breast cancer. Methods An independent, blinded review of radiologic and clinical data was performed, assessing progression and response according to Response Evaluation Criteria in Solid Tumors. In addition, ECOG's investigator assessments were reanalyzed using the same methods applied to the independent review. The primary end point was PFS as assessed by an independent review facility (IRF). Results The addition of bevacizumab to paclitaxel resulted in a statistically significant improvement in PFS using both the IRF and investigator assessments. Hazard ratios for PFS (0.48, 95% CI, 0.385 to 0.607; P < .0001 for the IRF v 0.42, 95% CI, 0.34 to 0.52; P < .0001 for ECOG investigators) and the improvement in median PFS (11.3 v 5.8 months for the IRF v 11.4 v 5.8 months for ECOG investigators) were similar. Among patients with measurable disease at baseline, the IRF-assessed ORR was significantly higher in patients treated with paclitaxel and bevacizumab (48.9% v 22.2%; P < .0001). Conclusion The risk of progression was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming a substantial and robust bevacizumab treatment effect. The consistency between the IRF and ECOG analyses validates the original data previously reported by ECOG in this open-label trial.

Phase III Trial of Sunitinib in Combination With Capecitabine Versus Capecitabine Monotherapy for the Treatment of Patients With Pretreated Metastatic Breast Cancer

2013 ◽  
Vol 31 (23) ◽  
pp. 2870-2878 ◽  
Author(s):  
John P. Crown ◽  
Véronique Diéras ◽  
Elzbieta Staroslawska ◽  
Denise A. Yardley ◽  
Thomas Bachelot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Metastatic breast cancer (MBC) remains an incurable illness in the majority of cases, despite major therapeutic advances. This may be related to the ability of breast tumors to induce neoangiogenesis, even in the face of cytotoxic chemotherapy. Sunitinib, an inhibitor of key molecules involved in neoangiogenesis, has an established role in the treatment of metastatic renal cell and other cancers and demonstrated activity in a phase II trial in MBC. We performed a randomized phase III trial comparing sunitinib plus capecitabine (2,000 mg/m2) with single-agent capecitabine (2,500 mg/m2) in patients with heavily pretreated MBC. Patients and Methods Eligibility criteria included MBC, prior therapy with anthracyclines and taxanes, one or two prior chemotherapy regimens for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. The primary end point was progression-free survival, for which the study had 90% power to detect a 50% improvement (from 4 to 6 months). Results A total of 442 patients were randomly assigned. Progression-free survival was not significantly different between the treatment arms, with medians of 5.5 months (95% CI, 4.5 to 6.0) for the sunitinib plus capecitabine arm and 5.9 months (95% CI, 5.4 to 7.6) for the capecitabine monotherapy arm (hazard ratio, 1.22; 95% CI, 0.95 to 1.58; one-sided P = .941). There were no significant differences in response rate or overall survival. Toxicity, except for hand-foot syndrome, was more severe in the combination arm. Conclusion The addition of sunitinib to capecitabine does not improve the clinical outcome of patients with MBC pretreated with anthracyclines and taxanes.

scholarly journals Dual HER2 Suppression with Lapatinib plus Trastuzumab for Metastatic Inflammatory Breast Cancer: A Case Report of Prolonged Stable Disease

2018 ◽  
Vol 11 (3) ◽  
pp. 855-860 ◽  
Author(s):  
Lauren Ogawa ◽  
Deborah Lindquist
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Stable Disease ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Bilateral Mastectomy ◽  
Targeted Agents ◽  
Open Label

Background: Continuous therapy targeting human epidermal growth factor receptor 2 (HER2) is recommended until disease progression for patients with HER2-overexpressing (HER2+) metastatic breast cancer. Prolonged stable disease has been observed with such maintenance therapy using trastuzumab, but the frequency of these cases remains low. Whether combined maintenance therapy with two different HER2-targeted agents could improve the rates of durable progression-free survival compared with trastuzumab alone is under investigation. Objectives: To evaluate the efficacy of the combined HER2-targeted agents, trastuzumab and lapatinib, as maintenance therapy in one patient. Methods: We describe a patient with HER2+, hormone receptor-negative, inflammatory metastatic breast cancer who was previously treated with doxorubicin, cyclophosphamide, and zoledronic acid followed by paclitaxel and trastuzumab. After completion, the patient underwent a bilateral mastectomy and then enrolled into a Phase III open-label clinical trial of trastuzumab plus lapatinib. Results: The patient experienced long-term stable disease on combined lapatinib and trastuzumab maintenance therapy over 4 years. Conclusions: This case demonstrates that prolonged stable disease is possible with lapatinib plus trastuzumab, even in patients with the aggressive inflammatory subtype. Optimization of maintenance therapy could improve outcomes for patients with HER2+ metastatic breast cancer.

Randomized Phase III Trial of Capecitabine Compared With Bevacizumab Plus Capecitabine in Patients With Previously Treated Metastatic Breast Cancer

2005 ◽  
Vol 23 (4) ◽  
pp. 792-799 ◽  
Author(s):  
Kathy D. Miller ◽  
Linnea I. Chap ◽  
Frankie A. Holmes ◽  
Melody A. Cobleigh ◽  
P. Kelly Marcom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Rates ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Treatment Groups ◽  
Previously Treated

Purpose This randomized phase III trial compared the efficacy and safety of capecitabine with or without bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. Patients and Methods Patients were randomly assigned to receive capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks, alone or in combination with bevacizumab (15 mg/kg) on day 1. The primary end point was progression-free survival (PFS), as determined by an independent review facility. Results From November 2000 to March 2002, 462 patients were enrolled. Treatment arms were balanced. No significant differences were found in the incidence of diarrhea, hand-foot syndrome, thromboembolic events, or serious bleeding episodes between treatment groups. Of other grade 3 or 4 adverse events, only hypertension requiring treatment (17.9% v 0.5%) was more frequent in patients receiving bevacizumab. Combination therapy significantly increased the response rates (19.8% v 9.1%; P = .001); however, this did not result in a longer PFS (4.86 v 4.17 months; hazard ratio = 0.98). Overall survival (15.1 v 14.5 months) and time to deterioration in quality of life as measured by the Functional Assessment Of Cancer Treatment—Breast were comparable in both treatment groups. Conclusion Bevacizumab was well tolerated in this heavily pretreated patient population. Although the addition of bevacizumab to capecitabine produced a significant increase in response rates, this did not translate into improved PFS or overall survival.

Sign in / Sign up

Export Citation Format

Share Document