Safety Of Eribulin Research Articles

Abstract OT3-1-04: A phase 2 study of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer (SONG-02)

Abstract Background: Pertuzumab, an anti-HER2 humanized monoclonal antibody that inhibits receptor dimerization, has a mechanism of action that is complementary to that of trastuzumab, and the combination of pertuzumab plus trastuzumab plus taxanes, when used as first-line treatment for HER2-positive metastatic breast cancer, significantly prolonged progression-free survival (PFS). However, in the second and later line treatment of HER2-positive advanced or recurrent breast cancer, it has not settled whether it should be treated with pertuzumab plus trastuzumab plus chemotherapy or with trastuzumab plus chemotherapy. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that has been proved to prolong the overall survival of advanced or recurrent breast cancer patients compared with the treatment of physician's choice. The benefit of eribulin in combination with trastuzumab for patients with locally recurrent or metastatic HER2-positive breast cancer has been reported. However, the efficacy and safety of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent HER2-positive breast cancer patients has not been reported. The purpose of this study is to evaluate the efficacy and safety of eribulin in combination with pertuzumab and trastuzumab as second and later line therapy for patients with advanced or recurrent HER2-positive breast cancer. Trial Design: This is a multicenter single arm phase 2 study for advanced or recurrent HER2-positive breast cancer patients who have experienced progression with anti-HER2 therapy. Patients received eribulin mesylate 1.4mg/m2 administered via intravenous (IV) infusion over 2 to 5 minutes on Days 1 and 8 each 21-day cycle and pertuzumab 840mg/kg IV and trastuzumab 8mg/kg IV over 90 minutes on Day 1 of Cycle 1. Thereafter eribulin mesylate 1.4mg/m2 and pertuzumab 420mg/kg and trastuzumab 6mg/kg was infused each 21-day cycle until disease progression or the appearance of toxic effects that could not be effectively managed. The primary endpoint is PFS of the combination therapy, based on local assessment of response using RECIST 1.1 criteria. Secondary endpoints are overall response rate (ORR), safety and tolerability. In addition, we examine PFS and safety according to the most recent treatment regimen. The study was conducted in accordance with the Declaration of Helsinki (2008), and the protocol and informed consent forms were submitted for approval to institutional review boards by the primary investigators. All patients provided written informed consent before undergoing any study-related procedures Statistical Method: All efficacy analyses were based primarily on the full analysis set (FAS), which included all patients who received over 1 dose(s) of study treatment. The PFS and ORR were calculated 95% confidence intervals (CIs). Treatment of 39 evaluable patients with the identified phase 2 doses will detect this difference with a power of 80% and alpha=5% (one-sided test). Accounting for a 10% invaluable rate and lead-in patients, a total of 43 patients will be enrolled on the study. Clinical trial information UMIN000014107. Citation Format: Hajime Abe, Shunji Kamigaki, Yoshifumi Komoike, Nobuki Matsunami, Yoshiaki Nakano, Kenji Tezuka, Junji Tsurutani, Jun Yamamura, Keiichi Yamazaki. A phase 2 study of eribulin in combination with pertuzumab and trastuzumab for advanced or recurrent human epidermal growth factor receptor 2 (HER2)-positive breast cancer (SONG-02) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-04.

Abstract P3-13-04: Efficacy and safety of eribulin in combination with capecitabine in patients with metastatic breast cancer: an open-label, phase II dose-confirmation study

Abstract Background: Two phase III trials have demonstrated the efficacy of eribulin monotherapy in patients with metastatic breast cancer (MBC) who have progressed after previous anthracycline and taxane chemotherapy. Capecitabine is also an effective agent in patients with MBC. A phase Ib dose-escalation study has investigated two dosing schedules of eribulin in combination with capecitabine to determine the recommended phase II dose. The aims of this open-label, non-randomized, phase II, dose-confirmation study were to determine efficacy and safety of this combination in patients with MBC. Interim data to April 2014 are provided here; final results will be presented at the meeting. Methods: Eligible patients were females with MBC who had received up to 3 previous chemotherapy regimens in any setting (including an anthracycline and a taxane, but excluding capecitabine), an ECOG performance status (PS) ≤1, and adequate hematological, renal and hepatic function (at study entry, 20 [47.6%] patients had liver metastases; 24 [57.1%] had lung metastases). Patients received 1.4 mg/m2 eribulin mesylate (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) i.v. on days 1 and 8 plus oral capecitabine 1000 mg/m2 b.i.d. on days 1–14 (21-day cycles) until disease progression, unacceptable toxicity or death. Disease assessments (CT scans) were performed every 6 weeks. The primary outcome was the objective response rate (ORR); secondary outcomes included clinical benefit rate (CBR), progression-free survival (PFS), and safety and tolerability. Results: 42 females (median age: 52.5 years [range: 32–74]; ECOG-PS of 0: n = 18 [42.9%]) were enrolled; patients received study drug as a 1st-line (23.8% [n = 10]), 2nd-line (45.2% [n = 19]) or ≥3rd-line (31.0% [n = 13]) chemotherapy. A median of 8 (range: 1–30) treatment cycles were administered (59.5% of patients received ≥6 cycles), with 94.4% of eribulin doses and 94.5% of capecitabine doses given as planned. The ORR was 42.9% and the CBR was 57.1% (Table), with a median PFS of 7.1 months (95% CI: 4.4, 9.8). The most common grade 3/4 adverse events (AEs) were neutropenia (66.7%), leukopenia (14.3%), febrile neutropenia (7.1%) and anemia, fatigue, nausea and peripheral sensory neuropathy (each 4.8%). AEs of special interest (any grade) included: hand–foot syndrome (26.2%), peripheral neuropathy (23.8%), and diarrhea (21.4%). The incidences of AEs leading to study drug dose adjustment were: 47.6% of patients (dose interruption), 42.9% (dose reduction), and 2.4% (drug withdrawal). Table: Tumor response (investigator assessment)PatientsN = 42n (%)n (%)Complete response (CR)2 (4.8)Partial response (PR)16 (38.1)Stable disease (SD)16 (38.1)Progressive disease (PD)3 (7.1)Not evaluable5 (11.9)Objective response rate (CR + PR)18 (42.9)95% CI27.7, 59.0Clinical benefit rate (CR + PR + SD ≥ 6 months)24 (57.1)95% CI41.0, 72.3 Conclusions: This phase II study suggests that eribulin in combination with capecitabine is efficacious in patients with MBC, with a safety and tolerability profile consistent with previous data. Phase III studies of this combination in patients with MBC are warranted. Citation Format: Chris Twelves, Muhammad Y Nasim, Alan Anthoney, Claudio I Savulsky, Shuxin Yin, TR Jeffry Evans. Efficacy and safety of eribulin in combination with capecitabine in patients with metastatic breast cancer: an open-label, phase II dose-confirmation study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-13-04.

Abstract P1-15-21: Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience

Abstract Background. Eribulin mesylate is a recently approved new therapeutic option for patients with metastatic breast cancer (BC). It is a structurally simplified synthetic analogue of halichondrin B that inhibits the growth phase of microtubule dynamics and sequesters tubulin into non-productive aggregates, inhibiting microtubule polymerization, and inducing irreversible mitotic block at G2-M phases and apoptosis. Three phase II trials of eribulin in chemotherapy pretreated advanced BC patients were completed. In all these studies, eribulin showed a manageable tolerability profile, with most of the common drug-related adverse events being neutropenia, fatigue, alopecia, nausea, and anemia, according to the phase I trials findings. Eribulin was also associated with an overall low incidence of peripheral neuropathy. When new chemotherapy options become available, one of the most important questions regarding the sequence of treatments is to address the safety of concomitant radiation treatments. Recently has been reported a clinical case treated with eribulin mesylate and whole-brain radiotherapy (RT) in a heavily pretreated patient with multiple visceral and bone metastases from triple negative breast cancer. In our knowledge this is the first analysis focusing on the safety of eribulin in patients concomitantly treated with palliative RT. Methods. All patients where heavily pretreated for metastatic breast cancer (≥4 previous chemotherapy lines), including anthracyclines and taxanes-based regimens. Patients received eribulin mesylate (1.4 mg/m2 i. v., on days 1 and 8, of a 21-day cycle). Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), every 8 weeks, or sooner if disease progression was suspected. Safety was assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Measures of bone-pain scores and analgesic consumption were evaluated at each visit, using a patient-rated scoring system. Results. Concerning 25 consecutive treated patients, median performance status at baseline was 2 (range 1-3). A median of 4 cycles of eribulin (range 2-10) were administered. All patients received palliative bone RT during eribulin treatment. No suspension or delay in chemotherapy administration was necessary. 20/25 cases underwent spinal bone irradiation; 8 Gy in single fraction was given in 13/25 patients, 12 cases received 20 Gy in 5 fractions. The overall response rate was 24% and the clinical benefit rate was 40%. Toxicity was manageable and in line with main published series; the most frequent grade 3 hematologic adverse events were neutropenia (56%), and anemia (20%). Bone pain scores fell within a few weeks and remained below baseline value throughout the analysis. The mean pain score was 2 at baseline and 0.7 at the end of observation period. The mean analgesic score was 1.8 at baseline and 1.6 at the end of follow-up. Conclusions. Our clinical practice experience supports the evidence that eribulin has clinical activity and is characterized by a manageable safety profile, also when combined to palliative RT. Concomitant treatment is feasible also in patients heavily pretreated, and with poor performance status. Citation Format: Icro Meattini, Vieri Scotti, Carla De Luca Cardillo, Beatrice Detti, Vanessa Di Cataldo, Lorenzo Livi. Safety of eribulin mesylate and concomitant palliative radiotherapy for metastatic breast cancer: A single-center experience [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-21.

P171 Efficacy and safety of eribulin as first- to third-line treatment with HER2(–) MBC (KBC-SG 1105)

P171 Efficacy and safety of eribulin as first- to third-line treatment with HER2(–) MBC (KBC-SG 1105)

Phase 2, Multicenter, Single-Arm Study of Eribulin Mesylate With Trastuzumab as First-Line Therapy for Locally Recurrent or Metastatic HER2-Positive Breast Cancer

BackgroundThe aim of this study was to assess efficacy and safety of eribulin with trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer. Patients and MethodsIn this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2+ breast cancer received eribulin mesylate at 1.4 mg/m2 intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary end point was ORR, and secondary end points included PFS, TTR, DOR, and safety. ResultsFifty-two patients were enrolled. Fifty-one patients (98.1%) had metastatic disease, 25 (48.1%) with liver metastases, 24 (46.2%) with lung metastases, and 19 (36.5%) with bone metastases. Patients received a median of 10.0 cycles of eribulin and 11.0 cycles of trastuzumab. The ORR was 71.2% (n = 37) with median TTR of 1.3 months, DOR of 11.1 months, and PFS of 11.6 months. The most common Grade 3/4 treatment-emergent adverse events were neutropenia in 20 (38.5%) patients, peripheral neuropathy in 14 (26.9%; all Grade 3) patients, fatigue in 4 (7.7%) patients, and febrile neutropenia in 4 (7.7%) patients. ConclusionsBecause of the high ORR, prolonged median PFS, and acceptable safety profile, combination eribulin/trastuzumab is an acceptable treatment option for locally recurrent or metastatic HER2+ breast cancer.

Phase 2 study of eribulin mesylate as first-line therapy for locally recurrent or metastatic human epidermal growth factor receptor 2-negative breast cancer

Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least 2 chemotherapeutic regimens for MBC that should have included an anthracycline and a taxane in the adjuvant or metastatic setting. This phase 2 study evaluated efficacy and safety of eribulin as first-line therapy for human epidermal growth factor receptor 2-negative (HER2-negative) MBC. Patients with measurable HER2-negative locally recurrent breast cancer or MBC with ≥12 months since prior neoadjuvant or adjuvant (neo/adjuvant) chemotherapy received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) per RECIST v1.1 (primary), safety, progression-free survival (PFS), clinical benefit rate (ORR + stable disease ≥6 months; CBR), and duration of response (DOR). Fifty-six patients were enrolled and received eribulin; 38 (68 %) had prior neo/adjuvant therapy, including 33 who had anthracycline and/or taxane-containing chemotherapy; 41 (73 %) had estrogen receptor-positive disease, and 12 (21 %) had estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) disease. Patients received a median of 7 cycles (range 1–43); 6 (11 %) received treatment for ≥12 months. ORR was 29 % (95 % CI 17.3–42.2), CBR was 52 %, and median DOR was 5.8 months. Median PFS was 6.8 months. Thirty-six patients (64 %) had grade 3/4 treatment-related adverse events; most common were neutropenia (50 %), leukopenia (21 %), and peripheral neuropathy (21 %). These results demonstrate that eribulin has substantial antitumor activity as first-line treatment for HER2-negative MBC with acceptable safety.

Abstract P4-12-12: Phase 2, multicenter, single-arm study of eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer

Abstract Background: Eribulin mesylate, a non-taxane microtubule dynamics inhibitor, has been approved for patients with metastatic breast cancer (MBC) who have previously received ≥2 chemotherapeutic regimens for MBC. We present final data from a phase 2 study that evaluated efficacy and safety of eribulin + trastuzumab as first-line therapy for locally recurrent or metastatic human epidermal growth factor receptor 2 positive (HER2+) BC. Methods: Patients received eribulin mesylate at 1.4 mg/m2 IV on days 1 and 8 of each 21-day cycle and an initial trastuzumab dose of 8 mg/kg IV on day 1, followed by 6 mg/kg on day 1 of each subsequent cycle. Endpoints include objective response rate (ORR), safety, progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 6-12 weeks thereafter per RECIST 1.1. Results: Fifty-two patients with a median age of 60 years (range 31- 81) were treated; 96% had stage IV disease, 73% had visceral disease, and 48% had liver metastases. Thirty one patients had prior neo/adjuvant chemotherapy (11 had prior anthracycline, and 22 had prior taxane). Patients received a median of 10(0, 33) cycles of eribulin and 11(1, 31) cycles of trastuzumab. ORR was 67% with median TTR of 1.3 months and PFS of 11.5 months (Table). The most common (>5%) Grade 3/4 treatment related treatment emergent (TRTE) AEs were neutropenia (n = 20; 38.5%), peripheral neuropathy (n = 14; 26.9%) and febrile neutropenia (n = 4; 7.7%). Serious TRTE AEs occurred in 14 patients and included neutropenia (n = 9; 17.3%), febrile neutropenia (n = 4; 7.7%), and peripheral neuropathy (n = 3; 5.8%). Reasons for discontinuation were AEs (n = 7) and PD (n = 22). Table. Summary of Efficacy EndpointsEfficacy EndpointsEribulin/Trastuzumab N = 52Objective Response Rate, n (%)35 (67)- Complete Response (CR)2 (4)- Partial Response (PR)33 (64)Stable Disease (SD)15 (29)Progressive Disease (PD)1 (2)Not Evaluable1 (2)Overall Clinical Benefit Rate, n (%)42 (81)Time to First Objective Response, median months (95% CI)1.3 (1.2, 1.4)Duration of Objective Response, median months (95% CI)a11.1 (6.5, 17.8)Progression-Free Survival, median months (95% CI)11.5 (7.3, 13.5)Duration of Stable Disease, median months (95% CI)7.1 (5.2, 13.5)Clinical Benefit Rate = ORR+ ≥6 mo SD; an = 35 Conclusions: This study suggests that the combination of eribulin + trastuzumab first-line therapy for locally recurrent or metastatic HER2+ BC has an acceptable safety profile and results in considerable tumor response with a long DOR. Additional larger studies with this combination are warranted. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-12.

Abstract P3-13-05: Eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer: Results of a phase 2, multicenter, single-arm study

Abstract Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least two chemotherapeutic regimens for MBC. We present final data from a phase 2 study that evaluated the efficacy and safety of eribulin as first-line therapy for HER2-negative (HER2-) MBC. Methods: Patients with measureable HER2- locally recurrent or MBC with ≥12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) (primary), safety, progression-free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 6-12 weeks thereafter per RECIST 1.1. Results: Fifty-six patients enrolled and received eribulin. Patients had a median age of 56 years (range 31-85); 32 (57%) had an ECOG status of 0; 17 (30%) had de novo stage IV; 33 (59%) had prior (neo)adjuvant therapy, including anthracycline and/or taxane (A/T) chemotherapy. Thirty-nine patients (70%) had visceral disease (45% liver, 32% lung); 41(73%) had estrogen receptor-positive (ER+) disease and 12 (21%) had triple negative (TN) disease. Thirty-two patients (57%) completed at least 6 cycles of treatment; among the 24 patients who completed fewer than 6 cycles, reasons for not completing were progressive disease (PD; n = 18), adverse events (AEs; n = 3) and patient choice (n = 3). The median number of cycles delivered was 7 (range 1-39); 6 patients (11%) received treatment for ≥12 months. Overall ORR was 27%, with median TTR of 1.4 months and median DOR of 7.4 months; stable disease (SD) rate was 48% (Table 1). Median PFS was 6.8 months. Thirty-five patients (63%) had grade 3/4 treatment-related AEs (Table 2). Treatment-related serious AEs occurred in 5 (9%) patients: neutropenia (5%), febrile neutropenia (5%), and leukopenia (2%). Conclusions: The results of this study suggest that first-line eribulin has antitumor activity in ER+/HER2- and TN MBC with safety consistent with the known profile. Further exploration of this treatment as part of earlier lines of breast cancer therapy, including neo/adjuvant, is warranted. Table 1. Summary of EfficacyEfficacyEribulin-treated patients N = 56ORR, n (%)15 (27)CR0PR15 (27)SD27 (48)PD12 (21)Clinical benefit rate (ORR + ≥6 mo SD)27 (48)Median months (95% CI) TTR1.4 (1.2, 2.7)DOR7.4 (4.7, NE)PFS6.8 (4.4, 7.4)NE, not estimable Table 2. Treatment-Related AEsAE (N = 56)All events (%)Grade 3/4 (%)Leading to study drug withdrawal1111Leading to dose reduction3427Common AEs (≥25%) Alopecia820Neutropenia7050Fatigue572Peripheral neuropathy5420Nausea460Anemia364Leukopenia3018Constipation270 Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-13-05.

Abstract P1-12-02: Results of a phase 2, multicenter, single-arm study of eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer

Abstract Background: Eribulin mesylate is a novel nontaxane microtubule dynamics inhibitor that is approved in patients (pts) with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. We are reporting a preliminary planned analysis (first 6 cycles of treatment) of a phase 2 study that evaluates efficacy and safety of eribulin as first-line therapy for HER2-negative MBC. Methods: Pts with measureable HER2-negative locally recurrent or MBC with at least 12 months since prior neoadjuvant or adjuvant chemotherapy received eribulin mesylate at 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments were evaluated every 6 weeks for the first 6 cycles and every 6–12 weeks thereafter per RECIST 1.1. Results: 54 of 56 enrolled pts had at least 1 post-baseline assessment. The median number of cycles delivered was 7 (range 1,21). Pt characteristics: median age, 56 yrs (range 31–85); ECOG of 0, 32 (57%); 29% had de novo stage IV; 38/56 (68%) had prior neo/adjuvant (45% had anthracycline and 45% taxane, the majority of which were given together). Seventy percent have visceral disease (45% liver, 38% lung); 41 (73%) have estrogen receptor-positive (ER) disease and 12 (21%) have triple negative (TN) (ER−/PR−/HER2−) disease. Objective response data are found in Table 1. The most common treatment-related AEs are reported in Table 2. Treatment-related serious AEs occurred in 5 (9%) pts, neutropenia (4%), and febrile neutropenia (5%). Five pts stopped study therapy due to adverse events. Fourteen pts remain on study treatment. Conclusions: The preliminary results of this first-line study suggest that eribulin has antitumor activity in ER+/HER2− and TN MBC with an acceptable safety profile. Further exploration of this treatment as part of neo/adjuvant therapy is warranted. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-12-02.

Abstract P5-20-04: Eribulin mesylate + trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer: results from a phase 2, multicenter, single-arm study

Abstract Background: Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, has been approved for patients with metastatic breast cancer (MBC) who have previously received at least two chemotherapeutic regimens for MBC. This study evaluates efficacy and safety of eribulin + trastuzumab (TRAZ) as first-line therapy for human epidermal growth factor receptor 2 positive (HER2+) locally recurrent or MBC. Methods: Patients received eribulin mesylate at 1.4 mg/m2 IV on days 1, 8 and TRAZ initial dose of 8 mg/kg IV on day 1 every 21 days, followed by 6 mg/kg on day 1 of each subsequent cycle. For study inclusion, patients could have been previously treated with TRAZ, but at least 12 months should have passed since any prior neoadjuvant or adjuvant chemotherapy was used. Endpoints include objective response rate (ORR) (primary), safety, progression free survival (PFS), time to response (TTR), and duration of response (DOR). Tumor assessments are evaluated every 6 weeks for the first 6 cycles and every 6–12 weeks thereafter per RECIST 1.1. Results: Updated results presented here as of June 1, 2012; 37 of 52 planned patients have been treated. Patient characteristics are as follows: median age: 58 years (range, 31–81), 70% have luminal subtype, 95% are stage IV disease, and 73% have visceral disease, 46% had prior neo/adjuvant, 22% had prior anthracycline and 32% had prior taxane, 35% had original diagnosis of MBC. Patients received median of 7 (1,20) cycles for eribulin and 9 (1,23) cycles for TRAZ. The most common treatment related AEs are reported in Table 1. Treatment-related serious AEs were reported for 4 (11%) patients; neutropenia 3 (8%) and febrile neutropenia 2 (6%) patients each. Eight patients have discontinued treatment due to disease progression (PD). Best patient responses are found in Table 2. Conclusions: Based on the updated preliminary results of this Phase II study, the combination of eribulin + trastuzumab as first-line therapy for HER2+ locally recurrent or MBC appears to demonstrate an acceptable safety profile with considerable tumor responses, including in patients with ER/PR+ disease. Accrual is ongoing and study completion is anticipated prior to SABCS 2012. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-20-04.

Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes

Eribulin inhibits microtubule dynamics via a mechanism distinct from that of other tubulin-targeting drugs, inducing cell-cycle arrest and tumour regression in preclinical models. We assessed the activity and safety of eribulin in four strata of patients with different types of soft-tissue sarcoma. In this non-randomised multicentre phase 2 study, patients were included if they had progressive or high-grade soft-tissue sarcoma and had received no more than one previous combination chemotherapy or up to two single drugs for advanced disease. They were stratified by the type of soft-tissue sarcoma they had. Eribulin was given intravenously at a concentration of 1·4 mg/m(2) over 2-5 min at days 1 and 8 every 3 weeks to primarily assess progression-free survival at 12 weeks (RECIST 1.0), which we evaluated in all patients who started treatment. Safety analyses were done in all patients who started treatment. This trial is registered at ClinicalTrials.gov, number NCT00413192. Of 128 patients included, 37 had adipocytic sarcoma, 40 had leiomyosarcoma, 19 had synovial sarcoma, and 32 had other sarcomas. 12 (31·6%) of 38 patients with leiomyosarcoma evaluable for the primary endpoint, 15 (46·9%) of 32 patients with adipocytic sarcoma, four (21·1%) of 19 with synovial sarcoma, and five (19·2%) of 26 in other sarcomas were progression-free at 12 weeks. The most common grade 3-4 adverse events were neutropenia (66 [52%] of 127 patients evaluable for safety), leucopenia (44 [35%]), anaemia (nine [7%]), fatigue (nine [7%]), febrile neutropenia (eight [6%]), abnormal alanine aminotransferase concentrations (six [5%]), mucositis (four [3%]), and sensory neuropathy (four [3%]). Eribulin deserves further study in this setting, based on progression-free survival at 12 weeks in leiomyosarcoma and adipocytic sarcoma. Eisai Limited, Hatfield, UK.

Abstract P6-13-02: Survival Outcomes with Eribulin Mesylate vs. Treatment of the Physician's Choice (TPC) in Heavily Pretreated Subjects with Locally Recurrent or Metastatic Breast Cancer in North America, Western Europe, and Australia: Results of the Phase III EMBRACE Study

Abstract Background: Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor. We conducted a randomized, controlled, open-label, phase III study to compare the efficacy and safety of eribulin vs. TPC in heavily pretreated subjects with locally recurrent or metastatic breast cancer. This report focuses on outcomes for participants enrolled in North America, Western Europe, and Australia (Region 1). Methods: Eligible subjects had locally recurrent or metastatic breast cancer and had received 2-5 prior chemotherapy regimens, including an anthracycline and a taxane, with ≥2 of the regimens given for locally recurrent or metastatic disease. Subjects were stratified by geographic region, HER2/neu status, and prior capecitabine treatment. They were randomized 2:1 to receive eribulin 1.4 mg/m2 intravenously over 2-5 minutes on Days 1 and 8 every 21 days or an approved TPC. The primary endpoint was overall survival (OS); progression-free survival (PFS) was a secondary endpoint. Results: A total of 762 subjects in 135 centers worldwide were enrolled. Subjects had a median age of 55 years, 92% were white, 76% were postmenopausal, and 81% had taxane-refractory disease. The median time since original diagnosis was 6.7 years. The majority of subjects (488 [64%]) were from Region 1, of whom 325 received eribulin and 163 received TPC. The most common treatments received by subjects from Region 1 in the TPC arm were vinorelbine (28%), gemcitabine (17%), capecitabine (13%), taxanes (20%), and anthracyclines (12%). 9% of subjects in this region received other therapies. Among the intent-to-treat population in Region 1, median OS was significantly prolonged with eribulin (13.3 months) vs. TPC (10.2 months) (HR: 0.724; 95% CI: 0.568-0.924; p=0.009). Median PFS was also prolonged with eribulin (3.3 months) vs. TPC (2.2 months; HR: 0.843; 95% CI: 0.666-1.066; p=0.153) in this population, as assessed by independent reviewers. Conclusion: OS was significantly prolonged in eribulin-treated patients participating in the EMBRACE trial in the North America, Western Europe, and Australia region. When assessed by independent review, PFS was also prolonged with eribulin, although this difference did not reach statistical significance for this geographic region. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-13-02.

Efficacy and safety of eribulin in Japanese patients (pts) with advanced breast cancer.

1081 Background: Eribulin mesylate (E7389) is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action currently in development for the treatment of advanced breast cancer and other solid tumors. This study evaluated the efficacy and safety of eribulin in Japanese pts with advanced breast cancer. Methods: This was a single-arm, open-label phase 2 study in pts with metastatic breast cancer (MBC) or locally advanced disease (RECIST measurable disease), ECOG performance status 0-2, previously treated with an anthracycline and a taxane. Pts had received ≤3 prior chemotherapy (CT) regimens in the metastatic setting, and either progressed within 6 months of their last CT or relapsed within 12 months of adjuvant or neoadjuvant CT. Eribulin mesylate (1.4 mg/m2) was administered as a 2-5 minute intravenous (IV) infusion on days 1 and 8 of a 21-day cycle. The primary efficacy endpoint was objective response rate (ORR; number of pts with complete response [CR] or partial response [PR] divided by t...