Trabectedin and Eribulin: Where Do They Fit in the Management of Soft Tissue Sarcoma?
Trabectedin and eribulin are two agents that have been recently approved for the treatment of specific soft tissue sarcoma subtypes. They have proved to be a much-needed line of additional treatment for patients with these rare tumors, but their activity remains admittedly modest in most cases. Further exploitation of these novel agents is likely to require a more granular understanding of the salient mechanisms of action. For example, if as some studies suggest, eribulin derives its benefit from restructuring of tumor vasculature to improve efficacy of subsequent lines of therapy, then patients may benefit from its use earlier in the treatment pathway. The sequencing of trabectedin with other agents is also worth examining. In a disease like myxoid liposarcoma, consideration should be given to using trabectedin before other salvage regimens like gemcitabine and docetaxel, given its tolerability and excellent efficacy against this sarcoma subtype. Also, to be further investigated is the use of trabectedin in sarcoma subtypes which were excluded from the phase III study, but in which activity has been documented in earlier trials and subsequent reports. Combinations of trabectedin with other agents, particularly doxorubicin, have been explored, but the data to date do not support the routine use of these regimens.
KeywordsSoft tissue sarcoma Trabectedin Eribulin Liposarcoma Leiomyosarcoma
Compliance with Ethical Standards
Conflict of Interest
Ravin Ratan declares that he has no conflict of interest.
Shreyaskumar R. Patel has received compensation from Janssen, Eisai, EMD-Serono, CytRx, Bayer, and Eli Lilly for service as a consultant, and financial support through grants from Janssen, Eisai, and Morphotek.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 7.Chuk MK, Aikin A, Whitcomb T, Widemann BC, Zannikos P, Bayever E, et al. A phase I trial and pharmacokinetic study of a 24-hour infusion of trabectedin (Yondelis(R), ET-743) in children and adolescents with relapsed or refractory solid tumors. Pediatr Blood Cancer. 2012;59(5):865–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Twelves C, Hoekman K, Bowman A, Vermorken JB, Anthoney A, Smyth J, et al. Phase I and pharmacokinetic study of Yondelis (Ecteinascidin-743; ET-743) administered as an infusion over 1 h or 3 h every 21 days in patients with solid tumours. Eur J Cancer. 2003;39(13):1842–51.CrossRefPubMedGoogle Scholar
- 10.•• Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009;27(25):4188–96. The phase III randomized trial that demonstrated the superiority of trabectedin over dacarbazine with respect to progression-free survival but not overall survival (its primary endpoint). This lead to FDA approval of trabectedin.CrossRefPubMedGoogle Scholar
- 11.Le Cesne A, Blay JY, Judson I, Van Oosterom A, Verweij J, Radford J, et al. Phase II study of ET-743 in advanced soft tissue sarcomas: a European organisation for the research and treatment of cancer (EORTC) soft tissue and bone sarcoma group trial. J Clin Oncol. 2005;23(3):576–84.CrossRefPubMedGoogle Scholar
- 13.Schwartz GK. Trabectedin and the L-Sarcomas: A Decade-Long Odyssey. J Clin Oncol. 2015.Google Scholar
- 17.Takahashi N, Li WW, Banerjee D, Scotto KW, Bertino JR. Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001;7(10):3251–7.Google Scholar
- 23.Pautier P, Floquet A, Chevreau C, Penel N, Guillemet C, Delcambre C, et al. Trabectedin in combination with doxorubicin for first-line treatment of advanced uterine or soft-tissue leiomyosarcoma (LMS-02): a non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2015;16(4):457–64.CrossRefPubMedGoogle Scholar
- 24.Martin-Broto J, Pousa AL, de Las PR, Garcia Del Muro X, Gutierrez A, Martinez-Trufero J, et al. Randomized phase II study of trabectedin and doxorubicin compared with doxorubicin alone as first-line treatment in patients with advanced soft tissue sarcomas: a Spanish Group for Research on Sarcoma Study. J Clin Oncol. 2016;34(19):2294–302.CrossRefPubMedGoogle Scholar
- 29.•• Schoffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016. This phase III randomized study demonstrated the overall survival benefit of eribulin over dacarbazine with respect to its primary endpoint of overall survival.Google Scholar
- 30.Chawla S, Schoffski P, Grignani G, Blay JY, Maki R, d'Adamo D, et al. Subtype-specific activity in liposarcoma (LPS) patients (pts) from a phase 3, open-label, randomized study of eribulin (ERI) versus dacarbazine (DTIC) in pts with advanced LPS and leiomyosarcoma (LMS). J Clin Oncol. 2016;34(suppl):Abstr 11037.Google Scholar
- 31.Young RJ. Woll PJ. Lancet: Eribulin in soft-tissue sarcoma; 2016.Google Scholar