... Since 2000, the soft tissue sarcoma treatment landscape has been reshaped by several important advances, not the least of which has been the development of drugs targeted for specific sarcoma subtypes. Arguably, one of the most important advances has been the identification, investigation and introduction of trabectedin to the armamentarium of drugs for refractory soft tissue sarcoma. Trabectedin is one of the first chemotherapeutic agents to be studied specifically for soft tissue sarcoma and the first agent since ifosfamide (in the early 1990s) to gain approval for use in the therapeutic setting of locally advanced or metastatic disease.
Marketed as Yondelis® (PharmaMar, S.A. Madrid, Spain), trabectedin is approved in more than 70 countries for treatment of advanced soft tissue sarcoma after failure of standard therapy with anthracyclines and ifosfamide, or in patients unsuited to receive these agents. Trabectedin in combination with PEGylated liposomal doxorubicin is also approved for treatment of patients with platinum-sensitive ovarian cancer.
In 2012, we marked the 13th year since trabectedin became available for investigation and celebrated the fifth anniversary of its gaining marketing approval for use in Europe.
During trabectedin’s history of use, several aspects of its unique profile have been revealed. Trabectedin is active in all soft tissue sarcoma histotypes and acts through a variety of mechanisms – from DNA repair, to displacement of transcription factors (important for selective sarcoma subtypes), through to immunomodulatory activity within the tumor microenvironment [2].
Perhaps just as importantly, trabectedin has taught us several things about our approach to the treatment of advanced soft tissue sarcoma. Trabectedin is the first agent to highlight the concept of prolonged tumor control. For the majority of patients with advanced soft tissue sarcoma, goals of treatment are long-term tumor stabilization with good quality of life. Trabectedin has paved the way for new models of care, including maintenance therapy and rechallenge after disease progression. Moreover, the unique pattern of tumor response to trabectedin (particularly in myxoid liposarcoma and leiomyosarcoma) has raised important queries about the appropriateness of conventional radiological evaluation of efficacy of chemotherapeutic agents according to Response Evaluation Criteria in Solid Tumors.
Numerous Phase II and III studies of trabectedin are underway in a bid to optimize its use in advanced soft tissue sarcoma; these are the focus of the current symposium. Owing in no small part to the introduction of trabectedin, it appears certain that the current standard-of-care paradigm in advanced soft tissue sarcoma is set for change.
...