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

Schöffski, Patrick; Ray‐Coquard, Isabelle; Cioffi, Angela; Nb, Bui; Bauer, Sebastian; Hartmann, J. T.; Krarup-Hansen, Anders; Grünwald, Viktor; Sciot, Raf; Dumez, Herlinde; Blay, Jean‐Yves; Cesne, Axel Le; Wanders, J.; Hayward, C.; Marréaud, Sandrine; Ouali, M.; Hohenberger, Peter

doi:10.1016/s1470-2045(11)70230-3

Cited by 216 publications

(153 citation statements)

References 12 publications

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“…Recently, the phase III trial comparing doxorubicin with doxorubicin/TH-302 completed accrual; results are pending. In addition, eribulin mesylate, a synthetic analogue of halichondrin B, a compound originally isolated from marine sponges, is currently being compared to dacarbazine in a pivotal trial in previously treated L-sarcomas based on the promising results of a previous EORTC phase II study [34]. Accrual for this trial has been completed and first results are expected in 2014.…”

Section: Treatment Of Patients With Advanced Diseasementioning

confidence: 99%

Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease

Schöffski¹,

Cornillie²,

Woźniak³

et al. 2014

Oncol Res Treat

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Sarcomas are a group of rare solid tumours arising from mesenchymal or connective tissue. This review focuses on soft tissue sarcoma and covers general topics such as the epidemiology, age distribution, site of disease, histogenesis, histological subtypes, prognosis and outcome of treatment. In more detail, the article reviews current systemic treatment standards and selected adverse events of agents such as doxorubicin, ifosfamide, trabectedin and pazopanib, and briefly highlights some drugs that are used off-label in specific subtypes of sarcoma.

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Section: Treatment Of Patients With Advanced Diseasementioning

confidence: 99%

Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease

Schöffski¹,

Cornillie²,

Woźniak³

et al. 2014

Oncol Res Treat

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“…Eribulin has broad anticancer activity in a wide variety of preclinical cancer models; as a result, numerous clinical trials of its effectiveness under monotherapy conditions are ongoing in other non-breast tumor types [4][5][6][7][8][9]. Although eribulin failed to show meaningful activities in clinical trials of head and neck, pancreatic and advanced non-small cell lung cancer [10,11], improvements in overall survival by eribulin were reported in a Phase 3 trial in advanced soft tissue sarcoma compared with dacarbazine [12], pointing to additional clinical uses for eribulin.…”

Section: Introductionmentioning

confidence: 99%

Identification of Combinatorial Drugs that Synergistically Kill both Eribulin-Sensitive and Eribulin-Insensitive Tumor Cells

Toshimitsu¹

2015

Glob J Cancer Ther

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Eribulin sensitivity was examined in a panel of twenty-five human cancer cell lines representing a variety of tumor types, with a preponderance of breast and lung cancer cell lines. As expected, the cell lines vary in sensitivity to eribulin at clinically relevant concentrations. To identify combination drugs capable of increasing anticancer effects in patients already responsive to eribulin, as well as inducing de novo anticancer effects in non-responders, we performed a combinatorial high throughput screen to identify drugs that combine with eribulin to selectively kill tumor cells. Among other observations, we found that inhibitors of ErbB1/ErbB2 (lapatinib, BIBW-2992, erlotinib), MEK (E6201, trametinib), PI3K (BKM-120), mTOR (AZD 8055, everolimus), PI3K/mTOR (BEZ 235), and a BCL2 family antagonist (ABT-263) show combinatorial activity with eribulin. In addition, antagonistic pairings with other agents, such as a topoisomerase I inhibitor (topotecan hydrochloride), an HSP-90 inhibitor (17-DMAG), and gemcitabine and cytarabine, were identified. In summary, the preclinical studies described here have identified several combination drugs that have the potential to either augment or antagonize eribulin's anticancer activity. Further elucidation of the mechanisms responsible for such interactions may be important for identifying valuable therapeutic partners for eribulin.of care. Chemotherapeutic drugs are often most effective when given in combination, in particular when synergistic killing is achieved without additive toxicity. To date, potential combination therapies for eribulin have been explored with only a limited number of anticancer agents. We therefore have performed an in vitro study of eribulin combined with 34 anticancer agents in 25 different tumor cell lines of various types, through use of a combination high throughput screening (cHTS) platform. Our goals were to identify drugs that might be paired with eribulin to increase clinical efficacy in metastatic breast cancer, to identify drugs that convert eribulin non-responders to responders, and to identify new therapeutic indications for eribulin utilization. Several compelling synergy effects with approved and emerging drugs were observed. The preclinical data provides insights about future clinical development strategies.

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“…The 12 week progressionfree in the liposarcoma stratum was 15/32 (46.9%) and for the leiomyosarcoma stratum 12/38 (31.6%). In contrast, the 12-week PFR in the synovial sarcoma stratum was 4/19 (21.1%) and for the other stratum 5/26 (19.2%) [44].…”

Section: Treatments In Development 41 Eribulinmentioning

confidence: 73%

Current and advancing systemic treatment options for soft tissue sarcomas

Harris

Benson

Jones

2015

Expert Opinion on Pharmacotherapy

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Much progression has been made in treatment of soft tissue sarcomas with multiple exciting new treatments in development. However outcomes in general remain poor. Further research into the underlying pathogenesis of soft tissue sarcomas may help deliver more effective systemic therapies. Increased collaboration between basic science, translational and clinical investigators is required at national and international levels to maximise progress.

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

Cited by 216 publications

References 12 publications

Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease

Soft Tissue Sarcoma: An Update on Systemic Treatment Options for Patients with Advanced Disease

Identification of Combinatorial Drugs that Synergistically Kill both Eribulin-Sensitive and Eribulin-Insensitive Tumor Cells

Current and advancing systemic treatment options for soft tissue sarcomas

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