Interim results of a real-world observational study of eribulin in soft tissue sarcoma including rare subtypes

Eisuke Kobayashi, Yoichi Naito, Naofumi Asano, Aiko Maejima, Makoto Endo, Shunji Takahashi, Yasunori Megumi, Akira Kawai, Eisuke Kobayashi, Yoichi Naito, Naofumi Asano, Aiko Maejima, Makoto Endo, Shunji Takahashi, Yasunori Megumi, Akira Kawai

Abstract

Background: Although eribulin is used to treat soft tissue sarcomas (STSs), treatment data for rare subtypes are limited. We conducted a post-marketing surveillance study to assess safety and efficacy of eribulin in STS patients stratified by subtype.

Methods: Japanese patients (n = 256) with advanced or metastatic STS receiving eribulin treatment were monitored for treatment status, adverse events, diagnostic imaging, and clinical outcomes at 3 months and 1 year. Interim analysis was performed. Patients will be monitored up to 2 years.

Results: Interim analysis included 3-month (n = 255), imaging (n = 226), and 1-year (n = 105) data. STS subtype distribution was normal. Median number of eribulin cycles was 3.0 (range: 1-17 cycles). Among patients with imaging data, best overall tumor response (12 weeks) was partial response, 7.5% (n = 17); stable disease, 34.5% (n = 78); and stable disease ≥11 weeks, 10.2% (n = 23). Overall response rate (ORR), disease control rate (DCR), and clinical benefit rate (CBR) for all patients were 7.5%, 42.0% and 17.7%, respectively. ORR, DCR, and CBR were 10.3%, 32.0% and 16.5%, respectively, for patients with STS subtypes other than liposarcoma and leiomyosarcoma and included responses from patients with rare STS subtypes. Adverse drug reactions (ADRs) occurred in 211 (82.7%) patients (42 [16.5%] patients had serious ADRs), and none led to death. ADRs leading to drug withdrawal and dose reduction occurred in 27 (10.6%) and 55 (21.6%) patients, respectively.

Conclusion: Eribulin was generally well tolerated and showed antitumor activity against STSs, including rare subtypes that currently have few treatment options.

Clinical trial number: NCT03058406 (ClinicalTrials.gov).

Keywords: Eribulin; post-marketing product surveillance; soft tissue sarcoma (STS).

© The Author(s) 2019. Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Treatment duration of eribulin in non-L-type soft tissue sarcoma patients. Response type and duration of eribulin treatment from start of treatment was plotted for patients with non-L-type soft tissue sarcoma for whom imaging data were available. Day 0 represents the start of treatment. Triangles indicate eribulin treatment was continued. Circles indicate eribulin treatment was discontinued. The number in the Y-axis column represents the number of prior CT. Abbreviations: SD, stable disease; PR, partial response; CT, chemotherapy.

References

    1. Blay JY, Sleijfer S, Schöffski P, et al. . International expert opinion on patient-tailored management of soft tissue sarcomas. Eur J Cancer 2014;50:679–89.
    1. Hatcher H, Benson C, Ajithkumar T. Systemic treatments in soft tissue sarcomas. Clin Oncol 2017;29:507–15.
    1. In GK, Hu JS, Tseng WW. Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations. Ther Adv Med Oncol 2017;9:533–50.
    1. Lilly [Internet] Lilly reports results of phase 3 soft tissue sarcoma study of LARTRUVO®. 2019. [cited 2019 May 16]. Available at:
    1. Tap WD, Wagner AJ, Papai Z, et al. ANNOUNCE: a randomized, placebo (PBO)-controlled, double-blind, phase (Ph) III trial of doxorubicin (dox) + olaratumab versus dox + PBO in patients (pts) with advanced soft tissue sarcomas (STS) [Abstract]. In: 2019 American Society of Clinical Oncology Annual Meeting; 2019 May 31–June 4; Chicago, IL. ASCO; 2019. Abstract LBA3.
    1. Schöffski P, Ray-Coquard IL, Cioffi A, et al. . Activity of eribulin mesylate in patients with soft-tissue sarcoma: a phase 2 study in four independent histological subtypes. Lancet Oncol 2011;12:1045–52.
    1. Asano M, Matsui J, Towle MJ, et al. . Broad-spectrum preclinical antitumor activity of eribulin (Halaven®): combination with anticancer agents of differing mechanisms. Anticancer Res 2018;38:3375–85.
    1. Schöffski P, Chawla S, Maki RG, et al. . Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet 2016;387:1629–37.
    1. Demetri GD, Schöffski P, Grignani G, et al. . Activity of eribulin in patients with advanced liposarcoma demonstrated in a subgroup analysis from a randomized phase III study of eribulin versus dacarbazine. J Clin Oncol 2017;35:3433–9.
    1. Setola E, Noujaim J, Benson C, et al. . Eribulin in advanced liposarcoma and leiomyosarcoma. Expert Rev Anticancer Ther 2017;17:717–23.
    1. Emambux S, Italiano A. Clinical efficacy of eribulin mesylate for the treatment of metastatic soft tissue sarcoma. Expert Opin Pharmacother 2017;18:819–24.
    1. Swami U, Shah U, Goel S. Eribulin in cancer treatment. Mar Drugs 2015;13:5016–58.
    1. Schöffski P, van Cann T, Cornilie J. Treatment options for anthracycline-resistant, advanced soft-tissue sarcoma: the role of eribulin. Expert Opin Orphan. Drugs 2017;5:445–53.
    1. Kawai A, Araki N, Naito Y, et al. . Phase 2 study of eribulin in patients with previously treated advanced or metastatic soft tissue sarcoma. Jpn J Clin Oncol 2017;47:137–44.
    1. The Pharmaceuticals and Medical Devices Agency , Japan [Internet]. Annual Report FY 2015 (April 2015–March 2016). 2015 [cited 2019 Feb 25]. Available from: .
    1. Kawai A, Yonemori K, Takahashi S, et al. . Systemic therapy for soft tissue sarcoma: proposals for the optimal use of pazopanib, trabectedin, and eribulin. Adv Ther 2017;34:1556–71.
    1. McGowan JV, Chung R, Maulik A, Piotrowska I, Walker JM, Yellon DM. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther 2017;31:63–75.
    1. Federal Drug Administration [Internet] Halaven (eribulin mesylate) Injection [cited 2019. Feb 25]. Available at: .
    1. Doyle LA. Sarcoma classification: an update based on the 2013 World Health Organization Classification of tumors of soft tissue and bone. Cancer 2014;120:1763–74.
    1. European Medicines Agency [Internet] HALAVIN, INN-eribulin [cited 2019. Feb 25]. Available at: .
    1. Watanabe J. Eribulin monotherapy improved survivals in patients with ER-positive HER2-negative metastatic breast cancer in the real world: a single institutional review. Springerplus 2015;4:625.
    1. Kolb EA, Gorlick R, Reynolds CP, et al. . Initial testing (stage 1) of eribulin, a novel tubulin binding agent, by the pediatric preclinical testing program. Pediatr Blood Cancer 2013;60:1325–32.
    1. Kawano S, Asano M, Adachi Y, et al. . Antimitotic and non-mitotic effects of eribulin mesilate in soft tissue sarcoma. Anticancer Res 2016;36:1553–61.
    1. De Vita A, Recine F, Mercatali L, et al. . Primary culture of undifferentiated pleomorphic sarcoma: molecular characterization and response to anticancer agents. Int J Mol Sci 2017;18:pii: E2662.
    1. Schoenfeld DA, Rosenbaum C, Horton J, Wolter JM, Falkson G, DeConti RC. A comparison of adriamycin versus vincristine and adriamycin, and cyclophosphamide versus vincristine, actinomycin-D, and cyclophosphamide for advanced sarcoma. Cancer 1982;50:2757–62.
    1. Bramwell VHC, Anderson D, Charette ML. Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline. Sarcoma 2000;4:103–12.
    1. Gronchi A, Ferrari S, Quagliuolo V, et al. . Full-dose neoadjuvant anthracycline + ifosfamide chemotherapy is associated with a relapse free survival (RFS) and overall survival (OS) benefit in localized high-risk adult soft tissue sarcomas (STS) of the extremities and trunk wall: Interim analysis of a prospective randomized trial. Ann Oncol 2016;27:Suppl_6.
    1. Frezza AM, Stacchiotti S, Gronchi A. Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new. BMC Med 2017;15:109.
    1. In GK, Hu JS, Tseng WW. Treatment of advanced, metastatic soft tissue sarcoma: latest evidence and clinical considerations. Ther Adv Med Oncol 2017;8:533–50.
    1. von Mehren M, Randall RL, Benjamin RS, et al. . Soft tissue sarcoma version 2.2018, Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2018;16:536–63.
    1. Penel N, Bui BN, Bay JO, et al. . Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol 2008;26:5269–74.
    1. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004;4:253–65.
    1. Jordan MA, Kamath K, Manna T, et al. . The primary antimitotic mechanism of action of the synthetic halichondrin E7389 is suppression of microtubule growth. Mol Cancer Ther 2005;4:1086–95.
    1. Smith JA, Wilson L, Azarenko O, et al. . Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry 2010;49:1331–37.
    1. Wada N, Uchi H, Furue M. Case of angiosarcoma of the scalp successfully controlled by eribulin. J Dermato 2018;45:116–7.
    1. Inagaki C, Shimoi T, Okuma H, et al. . A case of heavily pretreated metastatic cardiac angiosarcoma treated successfully using eribulin. Anticancer Drugs 2018;29:97–101.
    1. Iwai T, Hoshi M, Oebisu N, Shimatani A, Takada N, Nakamura H. Promising effects of eribulin for cystic lung metastases of epithelioid sarcoma: a case report. Anticancer Drugs 2018;29:806–9.
    1. Grounder MM, Ali S, Robinson V, et al. . Impact of next-generation sequencing (NGS) on diagnostic and therapeutic options in soft-tissue and bone sarcoma. J Clin Oncol 2017;35:11001–11001.
    1. Endo M, de Graff MA, Ingram DR, et al. . NY-ESO-1 (CTAG1B) expression in mesenchymal tumors. Mod Pathol 2015;28:587–95.
    1. Iura K, Maekawa A, Kohashi K, et al. . Cancer-tested antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Hum Pathol 2017;61:130–9.
    1. Thomas R, Al-Khadairi G, Roelands J, et al. . NY-ESO-1 based immunotherapy of cancer: Current perspectives. Front Immunol 2018;9:947.
    1. Aogi K, Iwata H, Masuda N, et al. . A phase II study of eribulin in Japanese patients with heavily pretreated metastatic breast cancer. Ann Oncol 2012;23:1441–8.
    1. Cortes J, O’Shaughnessy J, Loesch D, et al. . Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011;377:914–23.
    1. Ro J, Cheng FT, Sriuranpong V, et al. . Patient management with eribulin in metastatic breast cancer: a clinical practice guide. J Breast Cancer 2016;19:8–17.
    1. Ohtani S, Nakayama T, Yoshinami T, et al. . Bi-weekly eribulin therapy for metastatic breast cancer: a multicenter phase II prospective study (JUST-STUDY). Breast Cancer 2018;25:438–46.
    1. Kaufman P, Olivo M, He Y, McCutcheon S, Vahdat L. Peripheral neuropathy (PN) in patients (pts) with metastatic breast cancer treated with eribulin: Resolution and association with efficacy. J Clin Oncol 2014;32:147.
    1. Muss H, Cortes J, Vahdat LT, et al. . Eribulin monotherapy in patients aged 70 years and older with metastatic breast cancer. Oncologist 2014;19:318–27.
    1. Lesimple T, Edeline J, Carrothers TJ, et al. . A phase I, open-label, single-arm study for QT assessment of eribulin mesylate in patients with advanced solid tumors. Invest New Drugs 2013;31:900–9.

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