Phase II Clinical Trial of First-line Eribulin Plus Trastuzumab for Advanced or Recurrent HER2-positive Breast Cancer

Sakaguchi, Kôichi; Nakatsukasa, Katsuhiko; Koyama, Hiroshi; Kato, Masaaki; Sakuyama, Akira; Matsuda, Takayuki; Tsunoda, Nobuyuki; Fujiwara, Ikuya; Yamaguchi, Masahide; Tanaka, Hiroki; Onishi, Kazuyoshi; Onishi, Mie; Yoshino, Yūji; Kikuchi, Takashi; Taguchi, Tetsuya

doi:10.21873/anticanres.12697

Cited by 12 publications

(7 citation statements)

References 11 publications

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“…It is possible that suboptimal treatment of HER2-positive tumors could have induced negative results reported in the pivotal studies of EM in MBC. At the same time, phase II trials evaluating the combination of EM with anti-HER2 targeted therapies, such as trastuzumab [23][24][25] or the trastuzumab-pertuzumab doublet 26,27 reported a favorable safety profile, and interesting response rates, warranting additional investigations and a better definition of the place of such combinations in the HER2-positive MBC therapeutic strategy. of randomized trials to the general population.…”

Section: Discussionmentioning

confidence: 99%

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Jacot

Heudel

Fraisse

et al. 2019

Intl Journal of Cancer

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Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real‐life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression‐free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti‐HER2 targeted therapies use, we thus performed a subanalysis in HER2− patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to “Other chemotherapies” patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth‐line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth‐line). No significant difference was reported in second‐line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2− patients, a significant difference was seen for all lines, including 2nd‐line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real‐world database, HER2‐negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2‐targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti‐HER2 therapies addition in this setting still needs to be defined.

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Section: Discussionmentioning

confidence: 99%

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Jacot

Heudel

Fraisse

et al. 2019

Intl Journal of Cancer

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“…Several clinical studies have shown the efficacy and safety of trastuzumab and/or pertuzumab in combination with chemotherapeutic agents including docetaxel, paclitaxel, vinorelbine, and capecitabine in patients with HER2-positive MBC [ 6 – 8 , 31 – 34 ]. Recently, Sakaguchi et al conducted a multicenter, single-arm, phase II clinical trial of first-line eribulin and trastuzumab in 28 Japanese women with naïve progressive or recurrent HER2-positive breast cancer [ 35 ]. Patients received a median of 12 cycles (range, 2–53 cycles).…”

Section: Discussionmentioning

confidence: 99%

Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: a phase II, multicenter, collaborative, open-label, single-arm clinical trial

et al. 2019

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Summary Purpose To examine the efficacy and safety of triple therapy with eribulin, trastuzumab, and pertuzumab in patients with HER2-positive metastatic breast cancer (MBC) who never received any prior therapy in the first-line metastatic/advanced setting. Methods Eribulin 1.4 mg/m 2 (days 1 and 8), trastuzumab 8 mg/kg over 90 min and 6 mg/kg over 30 min, and pertuzumab 840 mg/body over 60 min and 420 mg/body over 30 min were administered intravenously in 21-day cycles. Results 25 women (median age, 57 years [range, 41–75 years]) received a median of 10 cycles (range, 0–34 cycles); 24 had performance status (PS) 0, 1 PS 1, 8 stage IV breast cancer, and 17 recurrence. Lung and liver metastases occurred in 9 and 9 patients, respectively. Median time to treatment failure with eribulin was 9.1 months (95% confidence interval [CI], 4.3–13.9 months), and median progression-free survival was 23.1 months (95% CI, 14.4–31.8 months). The overall response rate (complete response [CR] + partial response [PR]) was 80.0% (95% CI, 59.3–93.2%), and the clinical benefit rate (CR + PR + stable disease ≥24 weeks) was 84.0% (95% CI, 63.9–95.5%). The most common treatment-emergent adverse events (TEAEs) were alopecia (92.0%), fatigue (68.0%), and sensory peripheral neuropathy (60.0%). Grade 3/4 TEAEs occurred in 11 patients (44.0%). The only grade 4 TEAE was neutrophil count decreased (16.0%). Neither grade 4 peripheral neuropathy nor febrile neutropenia occurred. Conclusions ETP therapy showed acceptable efficacy and safety and is a potential first-line therapy for patients with HER2-positive MBC.

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“…Given the promising results of clinical trials with anti-HER2 agents in combination with conventional chemotherapies, the use of eribulin with trastuzumab was investigated in several studies. This combination was tested in a phase II trial for the first-line treatment of HE2-positive ABC and showed an ORR of 71.2% with a median PFS of 11.6 months ( Sakaguchi et al, 2018 ). Another phase II trial assessed the combination of eribulin with the dual antiHER2 block, trastuzumab and pertuzumab, in taxane-pretreated HER2-positive ABC, showing favourable outcome in terms of ORR and prolonged PFS ( Araki et al, 2017 ).…”

Section: Tubulin-binding Agentsmentioning

confidence: 99%

From seaside to bedside: Current evidence and future perspectives in the treatment of breast cancer using marine compounds

et al. 2022

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To date, only few marine natural compounds have been proved to be active in breast cancer (BC). The main marine-derived drugs that have been studied for the treatment of BC are tubulin-binding agents (eribulin and plocabulin), DNA-targeting agents (cytarabine and minor groove binders—trabectedin and lurbinectedin) and Antibody-Drug Conjugates (ADCs). Notably, eribulin is the only approved cytotoxic drug for the treatment of advanced BC (ABC), while cytarabine has a limited indication in case of leptomeningeal diffusion of the disease. Also plocabulin showed limited activity in ABC but further research is needed to define its ultimate potential role. The available clinical data for both trabectedin and lurbinectedin are of particular interest in the treatment of BRCA-mutated tumours and HR deficient disease, probably due to a possible immune-mediated mechanism of action. One of the most innovative therapeutic options for the treatment of BC, particularly in TNBC and HER2-positive BC, are ADCs. Some of the ADCs were developed using a specific marine-derived cytotoxic molecule as payload called auristatin. Among these, clinical data are available on ladiratuzumab vedotin and glembatumumab vedotin in TNBC, and on disitamab vedotin and ALT-P7 in HER2-positive patients. A deeper knowledge of the mechanism of action and of the potential predictive factors for response to marine-derived drugs is important for their rational and effective use, alone or in combination. In this narrative review, we discuss the role of marine-derived drugs for the treatment of BC, although most of them are not approved, and the opportunities that could arise from the potential treasure trove of the sea for novel BC therapeutics.

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Phase II Clinical Trial of First-line Eribulin Plus Trastuzumab for Advanced or Recurrent HER2-positive Breast Cancer

Abstract: Combination therapy of eribulin plus trastuzumab is acceptable in efficacy and safety, and a capable option for first-line advanced or recurrent HER2-positive breast cancer.

Cited by 12 publications

References 11 publications

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Real‐life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program

Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: a phase II, multicenter, collaborative, open-label, single-arm clinical trial

From seaside to bedside: Current evidence and future perspectives in the treatment of breast cancer using marine compounds

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