Safety Of Eribulin Research Articles

Eribulin plus carboplatin combination for HER2-negative metastatic breast cancer: a multicenter, real-world cohort study

BackgroundPre-clinical data suggests a potential synergistic effect of eribulin and platinum. However, clinical data on the combination for metastatic breast cancer (mBC) is lacking. We evaluated the efficacy and safety of eribulin plus carboplatin (ErCb) in patients with mBC.Patients and methodsThis multicenter, real-world cohort study included patients with pre-treated metastatic triple negative breast cancer (TNBC) or endocrine-refractory hormone receptor (HR) positive, HER2-negative mBC who received ErCb. Eribulin (1.4 mg/m2) and carboplatin (target AUC = 2) were administered intravenously on day 1 and 8 of 21-day cycle. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.ResultsFrom March 2022 to December 2023, a cohort of 37 patients were recruited to the study. Among them, 22 patients have TNBC and 15 have HR + HER2 − mBC. Of the 22 patients with TNBC, 8 had an initial diagnosis of the HR + HER2 − subtype. The median treatment was 6 cycles (range, 2 − 8 cycles). In the full cohort, TNBC, and HR + HER2 − subgroup, the ORR were 51.4%, 54.5% and 46.7%, the DCR were 81.1%, 81.8% and 80%, and the median PFS were 5 months, 5 months, and 5.2 months, respectively. The median OS was 12.7 months in the entire cohort and 12.8 months in TNBC subgroup. The most common grade 3/4 hematological AEs were neutropenia (37.8%), leukopenia (35.1%), febrile neutropenia (10.8%), thrombocytopenia (5.4%), and anemia (2.7%). No grade 3/4 non-hematological AEs were observed.ConclusionErCb demonstrated favorable efficacy and tolerability in patients with heavily pre-treated mBC, especially TNBC. The findings of the current study warrant further investigation of the application of this combination in earlier lines of mBC treatment.

Eribulin and irinotecan for refractory or recurrent Ewing sarcoma: A retrospective study.

e23502 Background: The effectiveness of eribulin and irinotecan in treatment of xenograft models of Ewing sarcoma is well-established but little clinical data has been reported. Encouraging results from preclinical models and a shortage of temozolomide in our hospital have prompted the administration of the eribulin as substitute for temozolomide and vincristine in combination of irinotecan at our institution from 2022 to 2023 in an off-label way. Methods: We retrospectively reviewed the medical records of patients treated for refractory or recurrent Ewing sarcoma with 1.4mg/m2 D1,8 eribulin and 20mg/m2/d D1-5,8-12 irinotecan at 21 day intervals (ERII) at Peking University People’s Hospital. Results: Finally, a total of 17 patients with median age 18.6 years were treated with a total of 77 courses of ERII between February 2022 and February 2023. The objective response rate was 35.3%, the disease control rate 58.9% and the median event-free survival (EFS) 2.07 months. 35.3% patients had 6 months EFS and overall survival was 66.9%. Grade 3 or 4 toxicities were observed in 37.6% courses and in 64.7% of the patients, with myelosuppression, especially neutropenia, being the most common and diarrhea / abdominal pain the second most common. In the dx5x2 VIT protocol the later portion was given two days after the end of early portion. However, in this substitute regimen of eribulin, the median time interval between the end of the early portion to the start of later portion was 5 days. The dose intensity of the regimen was reduced by 21% per cycle. The later portion was delayed mostly because of unrecovered myelosuppression. Conclusions: The efficacy and safety of eribulin and irinotecan as a second-line regimen was inferior to historical reports of temozolomide and irinotecan in the same institute. There was no need for further prospective trials on this combination unless mechanisms of synergy and biomarkers are identified. [Table: see text]

Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multicenter, open-label, single-arm, phase II study.

e13139 Background: The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 14 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 70 patients were enrolled from November 2021 to October 2023; 47 (71.4%) had HR+HER2- and 18 (28.6%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (68.6%), liver (52.9%), lymph nodes (48.6%), lung (44.3%) and brain (10.0%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 48.6%, the DCR was 92.9% and the median PFS was 7.2 months. For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 6.3 months. Among HR+ patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of HR+ patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. For the HR+ HER2-low subgroup, the median PFS was 8.4 months. The most common grade 3-4 AEs were hematological, including neutropenia (38.6%), leukopenia (31.4%), anemia (24.3%), and thrombocytopenia (15.7%). Grade ≥3 perceived AEs were relatively low. Conclusions: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]

Therapeutic Efficacy, Safety and Predictive Indicators of Eribulin Plus Anti-Angiogenic Medicine for Metastatic Breast Cancer.

To evaluate the efficacy and safety of eribulin plus anti-angiogenic medicine in metastatic breast cancer (MBC), and explore the potential biomarkers. Observational study. Place and Duration of the Study: Department of Medical Oncology, Xi'an International Medical Centre Hospital, Xi'an, China, from May 2022 to 2023. A total of 40 MBC patients treated with eribulin were enrolled. Patients were divided into two groups based on whether they received eribulin monotherapy or combined therapy. Median progression-free survival (mPFS), the time from the start of erbium treatment to the time of disease progression, was calculated using the Kaplan-Meier method. The eribulin plus anti-angiogenic medicine treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic medicine treatment (7.0 months vs. 2.0 months, p <0.001). The multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after the treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxane was predictive of shorter PFS (HR = 4.583, p = 0.019). Other clinic-pathological factors were not significantly associated with PFS. Fisher's exact test showed no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic medicine. The eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. Metastatic breast cancer, Eribulin, Anti-angiogenic therapy, Predictive indicators of efficacy.

Abstract PO3-05-10: Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II study

Abstract Background: Eribulin is a halichondrin non-taxane inhibitor of microtubule dynamics approved in China for advanced breast cancer patients who have received at least two prior chemotherapy treatments. The combination of eribulin and gemcitabine has demonstrated a similar progression-free survival (PFS) benefit as paclitaxel plus gemcitabine, with less neurotoxicity, for patients with MBC who have not received prior cytotoxic chemotherapy. However, the effect of eribulin plus gemcitabine on PFS in second line or beyond remains unclear. Methods: This open-label, single-arm, phase II study (NCT05263882) was conducted at 13 institutions in China. Eligible patients had histologically confirmed HER2-negative MBC and had received at least one prior taxane-containing chemotherapy regimen for advanced disease, and anthracycline-containing regimens in the adjuvant setting. Patients received intravenous infusions of eribulin (1.4 mg/m2) and gemcitabine (1.0 g/m2) on days 1 and 8 of a 21-day cycle. Efficacy outcomes, including PFS, objective response rate (ORR), and disease control rate (DCR), were assessed using RECIST v1.1. Adverse events (AEs) were graded according to NCI-CTC version 5.0. Results: A total of 65 patients were enrolled from November 2021 to May 2023; 47 (72.3%) had HR+/HER2- and 18 (27.7%) had triple-negative MBC. The median patient age was 50 years (range: 31-68), and the sites of metastasis were the bone (70.8%), liver (58.5%), lymph nodes (50.8%), lung (43.1%) and brain (10.8%). Patients had received a median of 3 prior lines of systemic treatment, 2 lines of chemotherapy, and 1 line of endocrine treatment. Among all patients, the ORR was 52.3%, the DCR was 92.3% and the median PFS was 7.6 months (Table). For the HR-positive subgroup, the median PFS was 8.4 months, while for the triple-negative subgroup, it was 7.6 months. Among patients who had received prior CDK4/6 inhibitor treatment, the median PFS was 7.2 months. In the subgroup of patients who had not received CDK4/6 inhibitor treatment, the median PFS had not been reached. The most common grade 3-4 AEs were hematological, including neutropenia (41.6%), leukopenia (33.9%), anemia (23.1%), and thrombocytopenia (15.4%). No grade ≥3 perceived AEs were reported. Conclusion: Eribulin plus gemcitabine was effective in heavily pretreated patients with HER2- MBC, while maintaining a predictable and manageable safety profile. Table. Summary of efficacy outcomes Citation Format: PeiJian Peng, Xiao-Lu Xu, Jin-Cai Zhong, Jin-Hui Ye, Zhi-Hui Wang, Hong Wang, Hong Lin, Cai-Wen Du, Guorong Zou, Jie Ouyang, Ying-Ying Shi, Fei Xu, Geng-Sheng Yu, Yong-Kui Lu, Yong-Xia Wang, Shi-En Cui, Lu-Zhen Li. Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer (MBC): A multi-center, open-label, single-arm, phase II study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-10.

Abstract PO2-05-12: Retrospective analysis on therapeutic efficacy and predictive indicators of eribulin plus anti-angiogenic drugs for metastatic breast cancer

Abstract Background: Eribulin has been widely used for the treatment of metastatic breast cancer (MBC). It has been found that eribulin can work in synergy with Bevacizumab or Anlotinib to achieve anti-angiogenic effects and possible synergistic enhancement. To optimize the efficacy of eribulin usage in late-line MBC patients, it is essential to delve deeper into the effects of combined treatments and gather more real-world clinical outcomes. Therefore, we evaluated the efficacy and safety of eribulin plus the anti-angiogenic drugs in late-line MBC patients. Objective: This study aims to retrospectively analyze the therapeutic efficacy and safety of eribulin plus anti-angiogenic drugs in treating metastatic breast cancer and explore predictive indicators of the therapeutic efficacy of eribulin in treating MBC. Methods: A retrospective review study was performed. 40 Patients diagnosed with MBC and treated with eribulin in Xi’an international medical center hospital from May 2020 to May 2021 were enrolled in this study. Patients were evaluable for this study and divided into two groups based on whether they received eribulin monotherapy or combined therapy. 22 patients were treated with eribulin monotherapy, and 18 were treated with eribulin and anti-angiogenic drugs (Bevacizumab and Anlotinib). Patients’ treatment parameters and characteristics were recorded. The Kaplan-Meier method was used to calculate the median PFS and corresponding 95% confidence interval (CI), and the Cox regression model was used for multivariate analysis of predictive indicators. The Fisher exact probability test was used to compare the difference in adverse reactions between the two groups, with a level of significance set at p-value &amp;lt; 0.05. Results: All study patients have an average of 5 treatment lines and a median progression-free survival (mPFS) of 4.2 months. The eribulin plus anti-angiogenic drug treatment group had a significantly prolonged mPFS compared to the group without anti-angiogenic drug treatment (7.0 months vs 2.0 months, p &amp;lt; 0.001, log-rank). Multivariate analysis identified that the combination of anti-angiogenic therapy (HR = 0.043, p = 0.004) and the occurrence of grade 3-4 neutropenia after treatment were two predictive factors for longer PFS (HR = 0.322, p = 0.009). In contrast, prior resistance to taxanes was predictive of shorter PFS (HR = 4.583, p = 0.019). Other factors, including age, Eastern Cooperative Oncology Group (ECOG) performance status, hormone receptor (HR) type, expression status, human epidermal growth factor receptor-2 (HER-2) expression status, Ki-67 level, number of metastatic lesions, and number of prior lines of Eribulin therapy, were not significantly associated with PFS. The results of Fisher’s exact test show that there was no significant increase in treatment-related adverse events (all grades) after combination with anti-angiogenic drugs. Conclusion: A combination of eribulin and anti-angiogenic therapy has significantly prolonged mPFS in the treatment of MBC patients. Other factors such as prior non-taxane resistance, grade 3-4 neutropenia occurrence after treatment, and combined anti-angiogenic therapy can be used as biomarkers for predicting treatment efficacy. The adverse events are manageable and the safety of combined therapy can be guaranteed. Therefore, the eribulin plus anti-angiogenic combination may act as a potential therapy for late-line MBC patients with clinically beneficial therapeutic effects. Keywords: metastatic breast cancer, eribulin, anti-angiogenic therapy, retrospective analysis Citation Format: Junmei Zhang, Xuezheng Wang, Hongjuan Du, Yan Xue. Retrospective analysis on therapeutic efficacy and predictive indicators of eribulin plus anti-angiogenic drugs for metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-05-12.

Abstract PO5-15-12: Spatial immune correlates of response to eribulin and pembrolizumab in metastatic triple negative breast cancer (mTNBC) on the ENHANCE1 trial

Abstract Background: PD-L1 is the only approved biomarker for pembrolizumab in metastatic breast cancer for response to combination chemo-immunotherapy. As it is not predictive of response in all cases, additional biomarkers are needed. Previously we have demonstrated that stromal tumor infiltrating lymphocytes (sTILs) are associated with response to therapy in patients treated with front-line combination chemoimmunotherapy on the ENHANCE-1 study with eribulin and pembrolizumab. However, sTILs was not predictive of response in patients treated with prior lines of chemotherapy in the metastatic setting. We used multiplexed immunofluorescence on whole slide images to characterize associations between specific immune populations and outcomes in patients treated prospectively on the ENHANCE-1 study. Methods: ENHANCE-1 was a single arm phase Ib/II trial which evaluated the efficacy and safety of eribulin and pembrolizumab in 167 patients (pts) with mTNBC who had received 0-2 prior lines of therapy (66 pts in the first line setting [stratum 1] and 101 pts with 1-2 prior lines of therapy [stratum 2]). 138 patient samples were evaluable for our study: 58 samples from stratum 1 and 80 samples from stratum 2. Objective response rate (ORR) was defined as percentage of pts with either complete response (CR) or partial response (PR) by RECIST 1.1. The ORR was 25.8% in stratum 1 and 22.5% in stratum 2 for the 138 patients analyzed. We utilized whole tissue sections and quantitative multiplexed immunofluorescence (qmIF) stained with: CD4, FoxP3, CD8, CD56 and pancytokeratin to characterize T-cells, NK cells and tumor cells. Halo (Indica labs) was used to segment and threshold cells for positive markers as well as to identify tumor and stromal tissue areas. Results: We found that the ratio of CD8+ to CD4+FoxP3+ T-cells were associated with response, irrespective of stratum (p=0.005). As biopsies were not required immediately prior to enrollment on ENHANCE-1, we also evaluated samples based on prior number of treatments since biopsy to enrollment. We found that only 58/138 patient samples evaluated were obtained without intervening treatment: 35 out of 58 from stratum 1 and 12 out of 80 from stratum 2. When samples were evaluated by stratum and the timing of tissue acquisition we found the ratio of CD8+ to CD4+FoxP3+ T-cells was more significantly associated with response (&amp;lt; 0.001) in patients whose sample were collected prior to enrollment, regardless of patient stratum. The ratio was not predictive in samples taken prior to treatments before enrollment. In addition, we found stromal and intratumoral CD8+ T-cell density is associated with response (p=0.02 and p=0.03 respectively) across both stratum. We did not find any significant changes assessed by qmIF in patient samples which had intervening treatment between sample collection and enrollment onto ENHANCE-1 trial. Conclusion: In this population of patients with mTNBC treated prospectively with eribulin and pembrolizumab, we find that a higher ratio of CD8+ to CD4+FoxP3+ T-cells and stromal and intratumoral CD8+ T-cell density is associated with response in patients with biopsy samples obtained prior to enrollment without intervening treatments after sample collection. The tumor microenvironment on patient samples obtained before one or more lines of therapy prior to enrollment on study are not predictive of response to treatment. Further characterization of the TME via quantitative immunofluorescence is ongoing. This study was funded by Eisai Citation Format: Matthew Kearney, Hua Guo, Rami Vanguri, Qi Wang, Eileen Connolly. Spatial immune correlates of response to eribulin and pembrolizumab in metastatic triple negative breast cancer (mTNBC) on the ENHANCE1 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-12.

Chemotherapy With Eribulin Following Potentially Curative Surgery in Patients With Localized Liposarcoma.

Soft tissue sarcomas are rare and heterogenous malignancies with high recurrence rates following resection and a poor prognosis in advanced stages. Eribulin is used in metastatic soft tissue sarcoma patients, who have failed first line chemotherapy and has been approved for patients with pretreated advanced liposarcoma (LPS) in the United States and Europe following the publication of data of a phase III trial. In addition, no data are available for eribulin as postoperative treatment after potentially curative surgery. We, thus, retrospectively evaluated efficacy and tolerability of adjuvant eribulin in patients with LPS not suitable for intensive chemotherapy in the routine clinical setting. In this retrospective single center analysis, efficacy and safety of eribulin were retrospectively evaluated in five high risk LPS patients. Eribulin as treatment was administered to five patients with LPS following surgical resection. Median progression-free survival and overall survival were 12.3 months and 44.3 months, respectively. Toxicity was generally manageable, and grade 3+4 events were rare. Postoperative eribulin may be feasible in selected high risk LPS patients, who are not candidates for intensive chemotherapy regimens. Further prospective trials, however, are needed.

63P Efficacy and safety of eribulin plus carboplatin combination for HER2-negative metastatic breast cancer

63P Efficacy and safety of eribulin plus carboplatin combination for HER2-negative metastatic breast cancer

1943P Efficacy and safety of eribulin plus anlotinib and camrelizumab in advanced or metastatic retroperitoneal liposarcoma (RLPS) or leiomyosarcoma (RLMS): A single-center retrospective cohort study

1943P Efficacy and safety of eribulin plus anlotinib and camrelizumab in advanced or metastatic retroperitoneal liposarcoma (RLPS) or leiomyosarcoma (RLMS): A single-center retrospective cohort study

Efficacy and safety of eribulin as a front-line treatment in patients with advanced breast cancer: The first large scale prospective real-world study in China.

e13127 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for third-line treatment of advanced breast cancer (ABC) in China in 2019. However, efficacy and safety data for eribulin in Chinese patients with ABC are lacking, regardless of the therapy line. This study evaluated the efficacy, safety, and treatment pattern of eribulin in first- to third-line settings in Chinese patients with ABC. Methods: Patients with histologically confirmed ABC who had received ≤2 lines of prior treatment for metastatic disease were enrolled. Patients with HR+/HER2- ABC received eribulin monotherapy; those with HER2+ ABC received eribulin plus anti-HER2 targeted therapy, and those with metastatic triple-negative breast cancer (mTNBC) received eribulin plus immunotherapy/chemotherapy. The primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: In total, 160 patients were enrolled from 1 January 2021 to 31 December 2022 and 142 received study treatment. Eribulin was administered as first-line therapy in 41 (28.9%) patients, second-line therapy in 50 (35.2%), and third-line therapy in 51 (35.9%). The DCR was 71.6%; 55 patients (45.8%) had stable disease and 31 patients (25.8%) had complete or partial remission. The 6-month PFS rates (95% confidence interval [CI]) were: overall, 68.4% (58.0%, 76.8%); first-line eribulin, 75.4% (54.9%, 87.6%); HR+/HER2- ABC, 67.4% (53.8%, 77.7%); HER2+ ABC, 70.1% (38.5%, 87.6%); mTNBC, 69.5% (46.3%, 84.2%). PFS data were immature; the median (range) PFS was not reached with first-line eribulin and was 11.8 (3.3, 11.8) months with second-line eribulin. Subgroup analyses are shown in the Table; the 6-month PFS rate was 64.3% versus 74.0% in patients with versus without visceral metastases (p=0.25364). Common treatment-related adverse events (AEs) were hematological toxicities including leukopenia (9.5%), neutropenia (5.3%), and hypochromia (7.3%). There were no grade ≥3 AEs or AE-related treatment discontinuations. Conclusions: There was no significant difference in the efficacy analysis between the subgroup with visceral metastases and the subgroup without visceral metastases. Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity in patients with ABC. Clinical trial information: NCT04683445 . [Table: see text]

Efficacy and safety of eribulin plus gemcitabine in second-line or beyond for patients with HER2-negative metastatic breast cancer: A multi-center, open-label, single-arm, phase II study.

e13102 Background: Eribulin is a non-taxane microtubule inhibitor approved in China for the treatment of patients with advanced breast cancer who progress after ≥2 lines of chemotherapy. Eribulin was shown to improve overall survival (OS) in various subgroups of patients with metastatic breast cancer (MBC) who were pretreated with an anthracycline and taxane. Furthermore, combination chemotherapy with eribulin plus gemcitabine led to a similar progression free-survival (PFS) benefit, with less neurotoxicity, as paclitaxel plus gemcitabine in patients with MBC who had not received prior cytotoxic chemotherapy for metastatic disease. However, the effect of eribulin plus gemcitabine on PFS in second-line or beyond remain unclear. Methods: This phase II, open-label, single-arm study was conducted at 13 institutions in China (NCT05263882). Patients with histologically confirmed HER2-negative MBC who had received at ≥1 prior taxane-containing chemotherapeutic regimen for advanced disease and had received anthracycline-containing regimens in the adjuvant setting, were enrolled between Nov 2021 and Oct 2022. Eligible patients received eribulin 1.4 mg/m2 and gemcitabine 1.0 g/m2 intravenously on days 1 and 8 of a 21-day cycle. Efficacy outcomes included PFS, objective response rate (ORR), and disease control rate (DCR), evaluated using RECIST v1.1. Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. Results: In total, 54 patients were included; 39 (72.2 %) were HR+/HER2- and 15 (27.8 %) were triple negative, the median age was 49.5 years (range: 31-70) and sites of metastasis were the liver (57.4%), lung (37.0%), bone (59.3%), brain (11.1%) and lymph nodes (53.7%). The median number of previous chemotherapy lines was 3 (range: 2-7): eribulin plus gemcitabine was used in second-line for 15 (27.8%) patients, third-line for 20 (37.0%) patients, fourth-line for 7 (13.0%) patients and ≥fifth-line in 12 (22.2%) patients. The median PFS was 7.7 months. The ORR was 40.7% and the DCR was 66.7%. Best overall responses and PFS rates at 3 and 6 months are shown. The most common grade 3-4 AEs were hematological: Leukopenia (35.2%), anemia (18.6%) and thrombocytopenia (9.4%). No treatment-related death was reported. Conclusions: Eribulin plus gemcitabine is effective in heavily pretreated patients with HER2-negative MBC with a predictable, manageable safety profile. Clinical trial information: NCT05263882 . [Table: see text]

Abstract P6-01-23: Role of tumor infiltrating lymphocytes and PD-L1 expression in the response to eribulin and pembrolizumab in metastatic triple negative breast cancer (mTNBC) on the ENHANCE1 trial

Abstract Background Treatment with combination chemo-immunotherapy has become the front-line standard for eligible patients with PD-L1 positive mTNBC. PD-L1 is the only approved biomarker for pembrolizumab in metastatic breast cancer for response to combination chemo-immunotherapy, however given that it is not predictive of response in all cases additional biomarkers are needed. Tumor infiltrating lymphocytes (TILs) have been shown to be both predictive and prognostic in operable TNBC, but there are fewer data regarding the role of TILs in mTNBC. In this study we report the associations between TILs and outcomes in patients treated prospectively on the ENHANCE-1 study with eribulin and pembrolizumab. Methods ENHANCE-1 was a single arm phase Ib/II trial which evaluated the efficacy and safety of eribulin and pembrolizumab in 167 patients (pts) with mTNBC who had received 0-2 prior lines of therapy (66 pts in the first line setting [stratum 1] and 101 pts with 1-2 prior lines of therapy [stratum 2]). Objective response rate (ORR) was defined as percentage of pts with either complete response (CR) or partial response (PR) by RECIST 1.1. The ORR was 25.8% in stratum 1 and 21.8% in stratum 2. Stromal TILs (sTIL) and intratumoral TILs were evaluated on whole slide H&amp;E sections from biopsy specimens used for enrollment on ENHANCE-1 by breast pathology according to the International TILs Working Group guidelines. PD-L1 positivity was determined via immunohistochemistry using the Agilent 22C3 antibody. We also assessed TIL density digitally using machine learning classifiers to identify tumor/stromal tissue areas and individual lymphocytes. Results We found that there was statistically significant increase in sTIL counts in responders compared to non-responders in stratum 1 (p=0.002) but not in stratum 2 (p=0.99). We did not find any associations between intratumoral TILs and response. Quantitative PD-L1 scoring via combined proportion score (CPS) was also positively associated with response in stratum 1 (p=0.01) but not in stratum 2 (p=0.34). We also find that sTIL counts are most correlated to CPS scores (continuous) for non-responders within stratum 1 (R2=+0.55, p&amp;lt; 0.01). Conclusion In this population of patients with mTNBC treated prospectively with eribulin and pembrolizumab, sTILs and PDL1 CPS were each individually associated with a positive response in patients treated with front-line combination chemo-immunotherapy. Neither was predictive for patient response in stratum 2. One important caveat is the biopsies were not required immediately prior to enrollment, possibly confounding the tumor microenvironment (TME) at the time of analysis. Our data contribute to emerging data that sTILs can act as a biomarker for response to immune checkpoint inhibition when utilized in the front-line setting for mTNBC. Further characterization of the TME via quantitative immunofluorescence is ongoing. This study was funded by Eisai IIS-E7389 Citation Format: Mathew Kearney, Hua Guo, Rami Vanguri, Qi Wang, Michelle Garlin, Courtney Connelly, Kevin Kalinsky, Eileen P. Connolly. Role of tumor infiltrating lymphocytes and PD-L1 expression in the response to eribulin and pembrolizumab in metastatic triple negative breast cancer (mTNBC) on the ENHANCE1 trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-23.

Eribulin in Patients with Liposarcoma and Leiomyosarcoma: A Retrospective Single-Center Experience

Introduction: Soft tissue sarcomas are rare and heterogenous malignancies with a poor prognosis in advanced disease stages. Eribulin is used in metastatic liposarcoma (LPS) patients, who have failed first-line chemotherapy and has been approved for use in patients with LPS in the USA and Europe due to its efficacy in this histological subtype in a phase 3 trial. We have evaluated efficacy and tolerability of eribulin in LPS and leiomyosarcoma (LMS) patients in the routine clinical setting at our department. Methods: In this retrospective single-center analysis, efficacy and safety of eribulin were retrospectively evaluated in advanced LPS and LMS patients at the Division of Oncology, Medical University of Vienna. Results: A total of 32 adult patients treated with eribulin were identified and included in this analysis. Overall response rate was 9.4% for all patients, with one patient with LPS and two patients with LMS showing a partial response. Disease control rate (partial response plus stable disease) for all patients was 50% (LPS: 47.1%; LMS 53.3%). No statistically significant difference in median progression-free survival and overall survival was detected between patients with LPS and LMS (p = 0.807 and p = 0.519, respectively). Patients with LMS (n = 2) had received fewer previous therapy lines than patients with LPS (n = 14) (≤ previous treatment lines, p < 0.001). Toxicity was generally manageable, and grade 3 + 4 events were rare. Conclusion: The activity and tolerability of eribulin in LPS as in well in LMS patients in the routine clinical setting is comparable to outcomes reported in published phase 3 trials.

Does the Timing of Eribulin Treatment for Advanced or Metastatic Breast Cancer Matter? Evidence from a Real-World Setting

Background: This study aimed to examine the effectiveness and safety of eribulin used as an early-line (EL, i.e., first-/second-line) versus late-line (LL, i.e., third-line and beyond) chemotherapy for recurrent advanced or metastatic breast cancer (A/MBC) patients. Methods: This study conducted a retrospective observation of A/MBC patients initiating eribulin between January 1, 2015, and June 30, 2019, using medical database at a university-affiliated teaching hospital in Taiwan. Patients were assigned into either the EL or LL group based on the timing of respective eribulin treatments and were observed for at least 6 months up to December 2019 for progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), disease response, and occurrence of adverse events. The Kaplan-Meier and Cox proportional hazard regression survival analyses were performed. Results: Of 127 patients, 23.6% (n = 30) and 76.4% (n = 97) were assigned to the EL and LL groups, respectively, between which no difference in patient characteristics was noted. Median PFS and TTF were 6.5 months and 5.0 months for the EL and 4.2 months and 3.4 months for the LL, respectively. Median OS could not be estimated in the EL group and was 20.5 months in the LL group. Eribulin as an EL treatment was the only factor associated with longer TTF and OS, whereas the number of metastatic sites was additionally associated with PFS in the multivariate analysis. No complete response was reported in either group, but a partial response was obtained in 6.7% in the EL group and 3.1% in the LL group. The common adverse events between two groups were similar, including leukopenia (80.0%), neutropenia (76.7%), and anemia (60.0%). Conclusions: The eribulin used as an EL of chemotherapy was effective for A/MBC patients with known toxicities in this study, while eribulin as the LL chemotherapy showed consistent results with previous reports.

Effectiveness and safety of eribulin as a front-line treatment in advanced breast cancer patients in China: A prospective real-world study.

e13015 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for the third-line treatment of advanced breast cancer (ABC) in China in 2019. However, the efficacy and safety data of eribulin for the ABC in Chinese patients is lacking, whether as first, second, or third-line regimens. This study aimed to evaluate the clinical effectiveness, safety, and treatment pattern of eribulin in first to third-line settings in Chinese ABC patients. Methods: Patients with histologically confirmed advanced breast cancer, who previously received ≤2 lines of treatment for metastatic disease were enrolled. In HR+/HER2- ABC, eribulin monotherapy was used; in HER2+ ABC, eribulin plus anti-HER2 targeted therapy were used; in metastasis triple-negative breast cancer (mTNBC), eribulin plus immunotherapy/chemotherapy were used. Primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: Forty-seven patients were enrolled from 2021.1.1 to 2021.10.20, including 41 metastatic and 6 de novo ABC patients. Eribulin was used as first-line therapy in 12 (25.5%) patients, second-line therapy in 24 patients (51.1%), and third-line therapy in 11 (23.1%) patients. More than 90% of the patients did not receive gemcitabine or vinorelbine, and 30.0% of them did not receive anthracycline or taxane previously. DCR was 70.2%, as 24 cases (51.1%) had stable disease and 9 cases (19.1%) had complete or partial remission. In subgroup analysis, median PFSs of 9.6 (95% CI: 6.5-12.7), 7.1 (95%CI: 4.4-9.8), and 5.6 (95%CI: 3.8-7.5) months were observed in patients receiving eribulin as first-, second-, and third-line therapy, respectively. In addition, median PFSs were 7.1 (95% CI: 5.1-9.3), 9.6 (95%CI: 3.6-15.7), 4.6 (95%CI: 4.6-4.6) and 5.8 (95%CI: 4.4-7.3) months for HR+/HER2-, HR+/HER2+, HR-/HER2+, and mTNBC patients, respectively. Other results from the subgroups analysis were shown in table. Common treatment-related toxicity was hematological toxicities including leukopenia (23%), neutropenia (17%), and thrombocytopenia (10%). There was no ≥grade 3 adverse events and no adverse event-related treatment discontinuation. Conclusions: Eribulin monotherapy or combined with targeted therapy was effective and well-tolerated as the first to third lines of treatment in ABC. This promising therapeutic outcome might warrant further studies in early eribulin administration in ABC patients. Clinical trial information: NCT04683445. [Table: see text]

Efficacy and safety of eribulin in the treatment of advanced adult soft tissue sarcoma (STS): First real-world data in Chinese population.

11577 Background: Eribulin has shown efficacy in STS, especially for the L-type sarcomas, including liposarcoma (LPS) and leiomyosarcoma (LMS). We investigated the efficacy and safety of eribulin in the treatment of advanced adult STS in Chinese population. Methods: The study retrospectively analyzed data from patients diagnosed as advanced STS and received eribulin monotherapy or combination regimens in the Department of Oncology, Zhongshan Hospital affiliated to Fudan University from January 2020 to February 2021. Primary endpoint was objective response rate (ORR) by RECIST v1.1. Secondary endpoints included disease control rate (DCR), progress-free survival (PFS) and treatment-related adverse events (TRAE) by CTCAE v5.0. Results: A total of 40 patients who received at least two doses of eribulin and underwent at least one post-baseline response assessment were included in analysis. The mean age was 48 years. 82.5% (33/40) had L-type sarcomas, and 17.5% (7/40) had non-L-type sarcomas. Overall, 25% (10/40) of patients received eribulin alone; and 75% (30/40) received combination regimens. Drugs used with eribulin included gemcitabine, tyrosine kinase inhibitors (TKIs), anti-PD-1 antibodies, or TKIs plus anti-PD-1 antibodies. For the 40 patients, the ORR was 27.5% (11/40) and the DCR was 60% (24/40). The ORR for myxoid liposarcoma was especially encouraging: 54.5% (6/11) and the DCR was 72.7% (8/11). 10 patients received the combined therapy of anti-PD-1 antibodies, TKIs, and eribulin and showed a likely better ORR of 30% (3/10) and DCR of 70% (7/10). After a median follow-up time of 12.57 months (IQR, 8.43-16.30), the median PFS was 4.13 months (95% CI, 2.17-8.40). 10 out of 33 (30.3%) patients with L-type sarcomas had achieved PR and the median PFS was 4.45 months, 1 out of 7 (14.3%) patients with non-L-type sarcomas had achieved PR and the median PFS is 2.67 months. Common TRAEs were bone marrow suppression (42.5%), hypertriglyceridemia (25%), fatigue (10%), hypertension (7.5%). No treatment-related death happened. Logistic regression analysis of the multiple factors influencing ORR revealed no difference between taxane-treated and taxane-naïve patient groups. Conclusions: This study presents the first real-world data on the use of eribulin in STS in Chinese population. Eribulin monotherapy or combination therapy were likely more effective in this population, as well-tolerated as with Study 309, especially in treating liposarcoma. Eribulin used in combination with TKI and anti-PD-1 antibody showed potential efficacy in STSs. Further clinical exploration of front-line eribulin monotherapy and combination strategies in this setting is warranted.

A phase II, multicenter, single-arm trial of eribulin in patients with bevacizumab-resistant recurrent glioblastoma.

2036 Background: Glioblastoma (GBM) is one of the worst prognostic cancers and there is no effective treatment after failure of bevacizumab. Eribulin is a microtubule inhibitor used for the treatment of patients with metastatic breast cancer and liposarcoma. We previously reported that eribulin strongly inhibits the RNA-dependent RNA polymerase (RdRP) activity of TERT protein in cancer cells, and has a strong anti-tumor effect against GBM cells with TERT promoter mutation. In this study we aim to investigate the efficacy and safety of eribulin in patients with bevacizumab-resistant recurrent GBM. Methods: This is an open-label, multicenter, single-arm phase II trial. Eligible patients aged 20-75 years with bevacizumab-resistant recurrent GBM were enrolled from 2018-2020. Patients received eribulin 1.4 mg/m2 on days 1 and 8 of 21-day cycle until disease progression or intolerable toxicity was observed. The primary endpoint was one-year overall survival rate (1yOS%). The 35 patients are needed to achieve an 80% power at a one-sided alpha of 10%, under threshold 1yOS% of 10% and expected 1yOS% of 25%. Results: Thirty-seven patients aged 26-73 (median: 54) years were treated. Twenty-six of 37 (70.3%) patients were diagnosed as IDH-wildtype GBM, 4 (10.8%) were with IDH-mutant GBM and 7 (18.9%) were GBM, NOS. Thirty-four (91.9%) patients had a Karnofsky performance status of 70 or 80 at the registration. Thirty-one (83.8%) patients received additional treatments, including 28 (75.7%) bevacizumab, 11 (29.7%) re-irradiation and 3 (8.1%) resection after failure of eribulin. Among 37 subjects, 32 surgical specimens were analyzed for TERT promoter mutation and 15 for RdRP activity. 1yOS% was 29.7% [80% CI: 20.5 to 39.5 (p &lt; 0.0001), 95% CI: 16.1 to 44.6]. Median OS was 9.0 months [95% CI: 6.2 to 11.0] and median progression-free survival was 1.5 months [95% CI: 1.4 to 1.7]. Neither TERT nor RdRP statuses was associated with prolonged OS. Among all the target lesions evaluated, two lesions decreased more than 50% in size and the patients survived more than one year, however no obvious PR was confirmed at the final evaluation. The disease control rate was 25.7% [95% CI: 12.5 to 43.3]. Common ≥ grade 2 AEs were neutropenia (70.3%), leukopenia (56.8%), lymphopenia (27.0%), elevation of γ-GTP (13.5%), elevation of ALT (10.8%), elevation of AST (8.1%), alopecia (8.1%). Treatment-related grade 3 or 4 AEs occurred in 59.5% of subjects. There were no AEs leading to death. Conclusions: Eribulin was safely applied for the patients with recurrent GBM. This phase II study met its primary endpoint of 1yOS%, although no obvious response was observed. Further investigation to reveal the biomarkers related to longer survival is underway. Clinical trial information: UMIN000030359.

Safety and effectiveness of eribulin in Japanese patients with soft tissue sarcoma including rare subtypes: a post-marketing observational study

BackgroundSoft tissue sarcomas (STSs) are a heterogeneous group of cancers with over 100 described subtypes. While these cancers are infrequent, the prognosis is quite poor, particularly for those with stage IV metastatic disease. Patients for whom curative resection is difficult or those with recurrent metastatic disease are treated with chemotherapy, although the options are very limited. Eribulin is an approved treatment of all STS subtypes in Japan. Efficacy and safety data for the treatment of rare STS subtypes other than liposarcoma and leiomyosarcoma (L-type sarcomas) are limited. This nationwide, multicenter, prospective, post-marketing observational study was conducted to assess the real-world effectiveness and safety of eribulin in Japanese patients with STS.MethodsPatients with all types of STS and who consented to eribulin treatment were eligible to participate. The observation period was 1 year, starting at treatment initiation, and clinical outcomes were followed up for 2 years after initiating treatment. The primary endpoint was overall survival (OS). Additional outcomes included time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. ORR and DCR were evaluated using imaging findings. Effectiveness results were analyzed both for all patients and by STS subtype.ResultsA total of 256 patients were enrolled; 252 and 254 were included in the effectiveness and safety analysis set, respectively. Most patients (83.1%) received an initial eribulin dose of 1.4 mg/m2 (standard dose). Respective median OS (95% confidence interval [CI]) was 10.8 (8.5–13.1), 13.8 (10.1–22.3) and 6.5 (5.7–11.1) months for all, L-type, and non-L-type subtypes. The respective median TTF (95% CI) was 2.5 (2.1–2.8), 2.8 (2.3–3.7), and 2.2 (1.6–2.6) months. The ORR and DCR were 8.1 and 42.6%, respectively. Adverse drug reactions (ADRs) and serious ADRs were reported for 83.5 and 18.9% of patients, respectively. The main ADRs were associated with myelosuppression. No significant difference was observed in the incidence of ADRs for patients ≥65 versus <65 years old.ConclusionsEribulin demonstrated effectiveness and a manageable safety profile for patients with STS, although the effectiveness of eribulin was not demonstrated for some non-L-type subtypes.Trial registrationNCT03058406 (ClinicalTrials.gov).

Efectividad y seguridad de la eribulina en la vida real en el tratamiento de cáncer de mama metastásico en un hospital general

ObjectiveTo assess efficacy (progression-free survival (PFS) and overall survival (OS)) and safety of eribulin in real clinical practice. MethodsObservational and retrospective study. Patients with metastatic breast cancer (mBC) treated with eribulin between 01/04/2014 and 31/10/2020 were included. Age, sex, ECOG performance status, HER-2, hormone receptor status, previous regimens for metastatic disease, previous ratio/hormone/surgical therapy, duration of treatment, toxicity and time to progression or death, were collected. Progression was evaluated by RECISTv1.1 criteria and toxicity by CTCAE.5.0 criteria. Statistical analysis was conducted by Log-Rank's test and Cox's Regression. Results38 patients were included, median age 57,6 years (±11,85), ECOG PS ≥ 2 (84,2%), negative HER2 overexpression (86,8%), hormone receptors expression (84,2%). All patients had already failed 2 chemotherapy regimens. Median duration was 4,35 months (IQR:2,44–6) and median cycles was 6 (IQR:4–8). Delays or reductions were 79% and 60,5%, respectively. Treatment was generally well tolerated, with 15.8% grade 3 and 10.5% grade 4 toxicities. 32 patients deceased, median OS 12,4 months (8,3-16,5). 37 had progressed, median PFS 6 moths (4,85-7,16). Log-Rank's test showed statistically significant difference in OS in patients with previous hormone therapy confirmed in Cox's regression [median 13,8 months (9.9–17.6); HR = 0,34 CI95%(0,12-0,98); p = 0,045 vs 6,5 months (6,1-6,9)]. ECOG PS > 2 showed better PFS in Log-Rank's Test and Cox's Regression [6,5 months (3,65-9,34); HR:0,35 CI95%(0,16-0,75); p = 0.038 vs 3,73 (0,09-7,38)]. ConclusionsEfficacy of eribulin in our real practice is similar to data from clinical essays observing statistically significant more OS in patients with previous hormone therapy and more PFS in ECOG's PS >2 subgroup and less incidence of grade 3/4-toxicity.