Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

scholarly journals Single arm, phase two study of low-dose metronomic eribulin in metastatic breast cancer

2021 ◽  
Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Peripheral Neuropathy ◽  
Clinical Benefit ◽  
Low Dose ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.

scholarly journals Efficacy and Safety of Eribulin in Taxane-Refractory Patients in the “Real World”

2016 ◽  
Author(s):  
Vito Lorusso ◽  
Saverio Cinieri ◽  
Agnese Latorre ◽  
Luca Porcu ◽  
Lucia Del Mastro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Peripheral Neurotoxicity ◽  
Eribulin Mesylate ◽  
Free Survival ◽  
Toxic Drugs

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8&ndash;3.5) and the median overall survival was 11.6 months (95% CI: 8.7&ndash;16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015

Chemotherapy ◽  
2017 ◽  
Vol 62 (5) ◽  
pp. 307-313 ◽  
Author(s):  
Jun Yamamura ◽  
Norikazu Masuda ◽  
Daigo Yamamoto ◽  
Shigeru Tsuyuki ◽  
Masahide Yamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival

Background: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. Methods: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. Results: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. Conclusion: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

scholarly journals Ixabepilone: Overview of Effectiveness, Safety, and Tolerability in Metastatic Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Nuhad K. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Management Strategies ◽  
Unmet Need ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Free Survival ◽  
Phase Iii Trials ◽  
Microtubule Stabilizer

Treatment algorithms for metastatic breast cancer describe sequential treatment with chemotherapy and, if appropriate, targeted therapy for as long as the patient receives benefit. The epothilone ixabepilone is a microtubule stabilizer approved as a monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer in patients with demonstrated resistance to anthracyclines and taxanes. While chemotherapy and endocrine therapy form the backbone of treatment for metastatic breast cancer, the epothilone drug class has distinguished itself for efficacy and safety among patients with disease progression during treatment with chemotherapy. In phase III trials, ixabepilone has extended progression-free survival and increased overall response rates, with a manageable toxicity profile. Recent analyses of subpopulations within large pooled datasets have characterized the clinical benefit for progression-free survival and overall survival for ixabepilone in special populations, such as patients with triple-negative breast cancer or those who relapsed within 12 months of prior treatment. Additional investigation settings for ixabepilone therapy discussed here include adjuvant therapy, weekly dosing schedules, and ixabepilone in new combinations of treatment. As with other microtubule stabilizers, ixabepilone treatment can lead to peripheral neuropathy, but evidence-based management strategies may reverse these symptoms. Dose reductions did not appear to have an impact on the efficacy of ixabepilone plus capecitabine. Incorporation of ixabepilone into individualized treatment plans can extend progression-free survival in a patient population that continues to represent an unmet need.

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.

Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1046-1046
Author(s):  
C. Mazouni ◽  
F. André ◽  
K. Broglio ◽  
L. Pusztai ◽  
G. N. Hortobagyi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Odds Ratio ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Rates ◽  
Free Survival ◽  
Er Positive

1046 Background:Differences in the efficacy of various chemotherapies in patients with estrogen receptor (ER) positive metastatic breast cancer are not well understood. In the present study, we assessed the efficacy of docetaxel in patients with metastatic breast cancer according to ER expression.Methods: The efficacy of docetaxel on response rates and progression-free survival were analyzed according to ER expression in four randomized trials that included a total of 1,631 patients. Odds-ratio for tumor response was estimated with logistic regression and hazard ratio for progression-free survival was estimated with Cox proportional hazards models. Results: ER expression was assessable in 1,037 patients included in these trials (64%). ER was expressed in 601 tumors (58%). Overall, docetaxel was associated with an increased response rate (odds ratio: 2.66, 95% CI: 1.83 to 3.87) and decreased hazard of disease progression (hazard ratio: 0.85, 95% CI: 0.73 to 0.97) compared to non-docetaxel containing therapy. Docetaxel was associated with similar improvement in response rate both in patients with ER-positive (odds ratio: 2.90, 95% CI: 1.72 to 4.87) and ER-negative disease (odds ratio: 2.55, 95% CI: 1.44 to 4.51). Among all ER-positive patients, tumor response rate was 31.1% among patients who did not receive docetaxel and 46.8% among patients who did receive docetaxel. Decreased hazard of disease progression due to docetaxel was also similar in ER-positive (HR: 0.82, 95% CI: 0.67–1.00) and ER-negative cancers (HR: 0.86, 95% CI: 0.70–1.07), but these results were heterogeneous among trials. The effect of docetaxel was not different in ER-positive and ER-negative disease, both in terms of response rates and progression-free survival (interaction test, p = 0.77 and p = 0.93). Conclusions: Docetaxel increases response rates and decreases the risk of disease-progression in a statistically similar extent both in patients with ER-positive and ER-negative metastatic breast cancer. No significant financial relationships to disclose.

Gemcitabine and Capecitabine Combination Chemotherapy in Patients with Metastatic Breast Cancer Pretreated with Anthracyclines and/or Taxanes

Chemotherapy ◽  
2016 ◽  
Vol 61 (4) ◽  
pp. 171-178 ◽  
Author(s):  
Guangyu Yao ◽  
Li Cao ◽  
Mingfeng Liu ◽  
Lujia Chen ◽  
Xiaolei Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Chemotherapy ◽  
Overall Response Rate ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Free Survival ◽  
Oral Capecitabine ◽  
Previously Treated

Background: Owing to the need for effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus capecitabine combination chemotherapy. Methods: Sixty-four patients were enrolled. Treatment consisted of gemcitabine 1,000 mg/m2 intravenously on days 1 and 8, plus oral capecitabine at 1,250 mg/m2 twice daily on days 1-14. The primary end point was the overall response rate (ORR). Secondary objectives included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors. Results: In the 64 patients, the ORR and DCR was 28.1 and 67.2%. Median OS and PFS were 23.6 and 13.4 months, respectively. Toxicities were mild and curable. Conclusion: The combination of gemcitabine and capecitabine is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes.

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