A phase III, open-label, randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes: Subgroup analyses.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1049-1049 ◽  
Author(s):  
Peter Andrew Kaufman ◽  
Javier Cortes ◽  
Ahmad Awada ◽  
Louise Yelle ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Randomized Study ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Her2 Status ◽  
Open Label ◽  
Eribulin Mesylate ◽  
Prior Chemotherapy ◽  
Metastatic Setting ◽  
Subgroup Analyses

1049^ Background: This phase III study, comparing eribulin versus capecitabine, showed a non-significant trend for superior overall survival (OS; hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.77, 1.00]; p = 0.056) but not progression-free survival (PFS; HR 1.08 [95% CI 0.93, 1.25]; p = 0.31). Pre-specified exploratory subgroup analyses previously presented showed that patients with triple-negative, ER-negative or HER2-negative disease may have a greater benefit in OS with eribulin compared with capecitabine. Here we present further pre-specified exploratory analyses of OS and PFS. Methods: Patients (eribulin n=554; capecitabine n=548) with locally advanced or MBC had received ≤3 prior chemotherapy regimens (≤2 for advanced disease), including an anthracycline and a taxane. Patients were randomized (stratified for geographic region and HER2 status) 1:1 to 21-day cycles of eribulin mesylate 1.4 mg/m2 i.v. on days 1 and 8 or capecitabine 1.25 g/m2BID orally on days 1-14. Further pre-specified exploratory subgroups included: age; receptor status; number and setting of prior chemotherapy regimen(s); sites of disease; number of organs involved; and time to progression after last chemotherapy. Results: From analyses for OS, patients with only non-visceral disease (HR 0.51; 95% CI 0.33, 0.80), with >2 organs involved (HR 0.75; 95% CI 0.62, 0.90), who had progressed >6 months after last chemotherapy (HR 0.70; 95% CI 0.52, 0.95), or who had received an anthracycline and/or a taxane in the metastatic setting (HR 0.84; 95% CI 0.72, 0.98), appeared to benefit more from treatment with eribulin compared with capecitabine. For OS, in no subgroup was a trend favoring capecitabine seen. Data for other pre-specified subgroups for both OS and PFS will be presented. Conclusions: In addition to patients with triple-, ER-, or HER2-negative disease, further pre-specified exploratory analyses suggest that other patient subgroups may particularly benefit from treatment with eribulin; further studies are warranted to address these hypotheses. Clinical trial information: NCT00337103.

scholarly journals Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

2015 ◽  
Vol 33 (6) ◽  
pp. 594-601 ◽  
Author(s):  
Peter A. Kaufman ◽  
Ahmad Awada ◽  
Chris Twelves ◽  
Louise Yelle ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Randomized Study ◽  
Objective Response ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Her2 Status ◽  
Open Label ◽  
Eribulin Mesylate

Purpose This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS.

A phase II, single-arm study of apatinib and oral etoposide in pretreated metastatic HER2-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1076-1076
Author(s):  
Nanlin Hu ◽  
Peng Yuan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Severe Toxicity ◽  
Oral Etoposide ◽  
Open Label ◽  
Prior Chemotherapy ◽  
Metastatic Setting

1076 Background: There is no standard treatment strategy for patients with locally advanced or metastatic breast cancer suffering progression after one prior chemotherapy with metastasis setting. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). Etoposide is a highly active chemo-drug in the treatment of advanced breast cancer, both as a single agent or in combination regimens, and is well tolerated, with a low incidence of severe toxicity. This study is performed to assessed the efficacy and safety of apatinib and oral etoposide in patients with HER2 negative locally advanced or metastatic breast cancer for whom at least one lines of prior chemotherapy had failed. Methods: This open-label, single arm study enrolled patients with HER2-negative breast cancer, pretreated with anthracycline, taxanes, and who failed in the metastatic setting at least one prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients. Apatinib was administered 425/500mg daily according to patients ECOG(Eastern Cooperative Oncology Group) status, oral etoposide was administered 50mg/m2 for first 10 days in a 21-days cycle. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. The treatment duration is until disease progression or intolerability of apatinib or oral etoposide. Results: 20 eligible patients were enrolled in this, open-label, single arm study and received apatinib and oral etoposide with a median age of 54 years old(range 36 to 66 years). Median follow-up time was 11months. 20 patients were eligible for efficacy analysis. Median PFS was 5.6 months (95% confidence interval (CI), 4.01 m – 8.42 m). ORR was 20% (4/20). DCR was 70% (14/20). Median OS was 11.2 months (95% CI, 9.6 m – 14.95 m). The most common grade 3/4 treatment-related AEs were hypertension (30%), and proteinuria (5%), nausea (5%). 35%(7/20) patients had dose reduction because of adverse events, after that all adverse events can return to less than 2 grade. Conclusions: Apatinib with oral etoposide exhibited objective efficacy in pretreated, metastatic HER2-negative breast cancer with manageable toxicity. Prospective studies enrolling more patients are needed. Clinical trial information: NCT03535961.

Phase III open-label, randomized, multicenter study of NKTR-102 versus treatment of physician's choice (TPC) in patients (pts) with locally recurrent or metastatic breast cancer (MBC) previously treated with an anthracycline, a taxane, and capecitabine (ATC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1140-TPS1140
Author(s):  
Edith A. Perez ◽  
Ahmad Awada ◽  
Joyce O'Shaughnessy ◽  
Hope S. Rugo ◽  
Christopher Twelves ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Topoisomerase I ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Rank Test ◽  
Continuous Exposure ◽  
Open Label ◽  
Metastatic Setting

TPS1140^ Background: NKTR-102 is a topoisomerase I inhibitor-polymer conjugate that hydrolyzes to provide continuous exposure to SN-38. A phase 2 trial of single-agent NKTR-102 was conducted in pts with 3rd-line MBC; 2 schedules (q14d; q21d) investigated a dose of 145 mg/m2. ORR was 29% (including 3% CR) with the prior ATC subset demonstrating an ORR of 31%. Dosing q21d was better tolerated; in this arm, median PFS and OS equaled 5.3m and 13.1m, respectively. Trial Design: Pts will be randomized 1:1 to receive single-agent NKTR-102 or TPC in an open-label, randomized, multicenter phase 3 study in pts with advanced breast cancer. Key Entry Criteria: Adult females, with ECOG 0 or 1 with adequate liver, kidney and marrow function. All pts must have received prior therapy with ATC (these drugs can be administered in the neo/adjuvant or locally advanced/metastatic setting). Prior A is not mandated if contraindicated. Prior toxicities must have resolved to ≤ Grade 1 (except sensory neuropathy ≤ Grade 2; complete resolution of prior diarrhea). Pts with brain metastases may be eligible, if lesions are stable for prior 3 weeks without steroids. Methods: Primary efficacy endpoint is OS. Secondary endpoints include: ORR by RECIST v1.1, clinical benefit rate (ORR+SD > 6 months), PFS and QoL. NKTR-102 is given IV at 145 mg/m2 over 90-min every 21 days without premedications. Pts randomized to TPC receive 1 of the following: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel or nab-paclitaxel (the agent must be available at the treating institution). Pts are stratified by region, prior eribulin and receptor status (TNBC, Her2+ or Other). Target Accrual: ~840 pts will be required for sufficient events to occur in the planned follow-up time; OS will be compared using a two-sided log-rank test; 1 interim analysis will occur when 50% of the deaths are reported. PK sampling is performed in a subset of pts. CTCs (isolated by Apocell ApoStream technology) are serially assessed for potential predictive markers of response and toxicity. Enrollment is expected to remain open until late 2013.

Quality of life (QoL) in patients (pts) with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes who received eribulin mesylate or capecitabine: A phase III, open-label, randomized study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1050-1050 ◽  
Author(s):  
Javier Cortes ◽  
Ahmad Awada ◽  
Peter Andrew Kaufman ◽  
Louise Yelle ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Side Effects ◽  
Hair Loss ◽  
Randomized Study ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Functional Domain ◽  
Treatment Change ◽  
Eribulin Mesylate ◽  
Patient Reported

1050^ Background: In a phase III trial comparing eribulin (E) vs. capecitabine (C) in pts with locally advanced or MBC, a trend for improved OS was observed but a statistically significant superiority was not demonstrated with E vs. C for OS or PFS. The AE profiles were consistent with known side effects. We now report QoL results from this trial. Methods: Pts received eribulin mesylate 1.4 mg/m2 on Days 1 and 8, or C 1.25 g/m2 BID orally on Days 1-14, of a 21-day cycle. Eligible pts had received prior therapy including an anthracycline and taxane, and were receiving study drug as 1st-, 2nd-, or 3rd-line therapy for advanced disease. QoL, a secondary objective, was assessed using EORTC QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks, 3, 6, 12, 18, and 24 months after starting treatment (or until progressive disease or treatment change), and at unscheduled visits. Longitudinal analyses were carried out using weighted generalized estimating equations adjusted for non-random attrition due to death within 12 months. Model covariates were time (visit), region, and baseline QoL. The primary endpoint was change from baseline for Global Health Status (GHS)/overall QoL; exploratory endpoints were change from baseline for each functional domain, and signs/symptoms. Results: 1,102 pts were randomized (E 554; C 548). GHS/QoL scores were low at baseline for E (56.3) and C (54.7) on a scale of 0 (worse) to 100 (best). GHS/QoL and cognitive functioning improved significantly more in pts receiving E vs. C, (6.5 [p=0.048] and 15.3 [p<0.001], respectively). Emotional functioning improved significantly for pts receiving C vs. E (3.3; p=0.033). Pain was comparable at baseline, and was lower at subsequent visits with both treatments. Patient-reported signs/symptoms in favor of E included nausea and vomiting (E1.9; p=0.043) and diarrhea (-3.7; p=0.001); systemic side effects (5.2; p<0.001) and upset by hair loss (9.3; p=0.023) favored C. Conclusions: GHS/QoL scores improved more in pts receiving E than C. E showed advantages in terms of gastrointestinal effects while C had advantages in relation to hair loss. Clinical trial information: NCT00337103.

A randomized phase III study to determine the efficacy of capecitabine in addition to a taxane and bevacizumab as first-line therapy in patients with metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1082-1082 ◽  
Author(s):  
Hans-Joachim Lueck ◽  
Kristina Luebbe ◽  
Joachim Bischoff ◽  
Nicolai Maass ◽  
Gabriele Feisel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Locally Advanced ◽  
Sample Size Calculation ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Open Label ◽  
Serious Adverse Events ◽  
Line Therapy

1082 Background: Conventional chemotherapy combined with novel molecular targeted agents has been proven effective and tolerable in metastatic breast cancer (MBC). Taxanes (T) plus bevacizumab (B) and T plus capecitabine (X) showed a benefit in progression free survival (PFS) compared to T alone. Life-threatening or highly symptomatic situations require poly-chemotherapies in MBC patients; therefore a combination of all 3 drugs appears reasonable. Methods: TABEA (NCT01200212) is a prospective, randomized, open label, phase III trial comparing T plus B +/- X as 1st-line therapy in MBC. Patients with histologically confirmed HER2- locally advanced or MBC were included. All patients received T (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) and B (15 mg/kg i.v. d1 q22) (TB) and were randomized to X (1800 mg/m² daily d1-14 q22) in addition and concurrently to TB (TBX) or TB alone. Randomization was stratified by receptor status, planned taxane, and disease free interval (≤ or >12 months). Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (CR, PR, stable disease ≥ 24 weeks), 3yr overall survival, PFS in patients ≥ 65 years, toxicity, and compliance. Sample size calculation assumed a PFS of 10 and 13.3 months for TB and TBX, respectively (HR=0.75) requiring 432 patients and 386 events with 2-sided α=0.05 and β=0.2. Interim analysis was planned after 25% of required events (n=96). Results: Planned interim futility and safety analyses after 100 documented events in 202 patients have shown no efficacy benefit and higher toxicity in the TBX arm. For PFS, HR=1.061, 95% CI (0.715, 1.576) was observed, futility boundary was crossed. Overall grade 3-4 adverse events (e.g., thrombopenia, diarrhea, hand-foot-syndrome) (72.3 vs. 57.4%, p=0.039)and serious adverse events (40.6 vs. 24.8%, p=0.016) rates were higher for TBX after 16.3 months median follow up. There were 6 deaths in the TBX vs. 1 in the TB arm. Recruitment and therapy were stopped on 5th Oct 2012 following the advice from the IDMC. Conclusions: TABEA failed to show an improvement using the 3 drug regimen TBX in high-risk MBC patients. Clinical trial information: NCT 01200212.

A phase II open-label trial to evaluate the efficacy and toxicity of erlotinib in women with metastatic, hormone receptor-negative, and HER2-negative breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 296-296
Author(s):  
R. D. Rao ◽  
K. P. Siziopikou ◽  
M. A. Cobleigh
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Stable Disease ◽  
Kinase Inhibitors ◽  
Metastatic Breast ◽  
Open Label ◽  
Prior Chemotherapy ◽  
Egfr Expression ◽  
Metastatic Setting ◽  
Egfr Tki

296 Background: There is limited success with current therapies for triple negative (TN) breast cancer. Epidermal growth factor receptor (EGFR) is a therapeutic target in solid tumors. Overexpression of EGFR has been linked to an aggressive breast tumor phenotype with a poor prognosis. Previous work at RUSH showed that 64% of 66 TN tumors were EGFR positive (Siziopikou SABCS 2004). To date, the use of EGFR tyrosine kinase inhibitors (TKIs) in metastatic breast cancer (MBC) has been disappointing. These trials enrolled refractory patients and did not select for EGFR expression. We hypothesized that if selected for EGFR expression, there may be a cohort of TN MBC patients who benefit from an EGFR TKI. This is a phase II study of erlotinib in TN-EGFR-positive MBC. Methods: Eligible patients had TN-EGFR-positive MBC. EGFR positivity was defined as staining in >10% of tumor cells by IHC (Dako). Patients required measurable disease, prior treatment with anthracycline and taxane (adjuvant or metastatic setting) and ≤1 prior chemotherapy for MBC. Patients received erlotinib 150mg daily. Primary endpoint was progression-free survival (PFS). Initially, 18 patients were to be accrued. If ≥ 3 patients were progression-free at 4 months, accrual would continue to 43. Results: The study was terminated prematurely due to poor accrual. In total, 11 patients enrolled, 10 were treated. Mean age 56.7y, 18% African-American. Four patients had prior chemotherapy for MBC. Most patients progressed rapidly, median PFS was 29 days (95% CI 25.90 – 32.10). However, 2 patients had stable disease for 225 and 476 days. Treatment was well-tolerated. Toxicities in the 2 patients with stable disease included grade 2 rash, grade 1 diarrhea, grade 1 nausea, grade 2 weight loss and grade 1 diarrhea. Conclusions: Although most patients progressed rapidly, 2/10 patients had prolonged stable disease. This suggests there may be a subset of TN, EGFR positive MBC for whom EGFR-directed therapy may be suitable or that the natural history of their disease was indolent. Future studies to determine molecular and clinical profiles of patients likely to benefit from EGFR-TKI therapy in this population are warranted.

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