La FDA pedía PFS como objetivo Primario y a la hora de evaluar exigio OS ... J&J se vieron obligados en EEUU a Realizar Fase III Sarcoma ... y a volver a repetir la Fase III Ovario ...
Una vez terminada la Fase III Sarcomas consiguio ser Aprobado por fin en EEUU el año pasado ... y en el caso de Ovario continua en curso la Fase III ya en la recta final :
|Estimated Primary Completion Date:||September 2018 .|
Expert Opin Pharmacother. 2017 Jan 31.
The Efficacy of Trabectedin in Treating Ovarian Cancer.
Teplinsky E1, Herzog TJ2.
Author information :
1 : Assistant Professor, Hofstra Northwell School of Medicine, Monter Cancer Center, Don Monti Division of Hematology & Medical Oncology , 450 Lakeville Road, Lake Success , NY 11042.
2 : Deputy Director, University of Cincinnati Cancer Institute, Paul & Carolyn Flory Endowed Professor, Vice Chair- Quality and Safety, Dept. of Obstetrics and Gynecology, Medical Sciences Bldg. Suite 2005H, ML 0662, 231 Albert Sabin Way University of Cincinnati , Cincinnati , Ohio 45267-0662.
The majority of women with epithelial ovarian cancer present with advanced stage disease and as such, there is a critical need for novel drugs and treatment strategies to improve outcomes in ovarian cancer. Trabectedin is a unique cytotoxic agent with a complex mechanism of action. It binds to guanines in the N2 position in the minor groove of DNA and its cytotoxicity involves DNA repair pathways and transcription regulation. Trabectedin's activity is also related to the drug-induced changes of the tumor microenvironment. It has been shown to improve progression-free survival in combination with pegylated liposomal doxorubicin in patients with platinum-sensitive relapsed ovarian cancer. The most common adverse events experienced with trabectedin are nausea, vomiting, fatigue, neutropenia and transaminitis. Studies of biomarkers that are predictors of trabectedin benefit are underway. Areas Covered: This review covers trabectedin's mechanism of action and pharmacology, the clinical development of the drug in ovarian cancer, ongoing trials, a
Trabectedin has received approval recently for leiomyosarcomas and liposarcomas following prior anthracycline chemotherapy in the USA.
The OVA-301 trial showed a PFS benefit for the combination of trabectedin/PLD versus PLD alone in platinum sensitive relapsed ovarian cancer but there was no survival benefit observed . " It is important to note that PFS, and not OS, was the primary objective of the study ".
However, a survival benefit was seen in patients who were considered partially platinum-sensitive with a PFI of 6-12 months and this is where trabectedin's potential use primarily lies. Obviously, those who are not good candidates for additional platinum-based therapy due to toxicity or hypersensitivity may potentially benefit from this agent as well. It is important to consider the results of OVA-301 in combination with the preclinical data demonstrating that trabectedin resistance may result in increased sensitivity to platinum agents as well as the long held belief by some that artificial prolongation of the PFI with a non-platinum based therapy results in clinical benefit. This further supports the use of trabectedin in this subpopulation. Although the MITO8 trial certainly has its limitations, it does start to challenge this concept, which will be addressed in the very important INOVATYON study. The biggest challenge currently lies in identifying the best patient population who can benefit from trabectedin. As the field of oncology progresses, it has become evident that biomarkers of predictive efficacy are needed to personalize treatment decisions.
Trabectedin has demonstrated increased activity in some settings where homologous recombination deficiency is present. Biomarkers predicting activity are being studied as translational components for the current phase III trials in recurrent ovarian cancer. The availability and use of trabectedin will be largely predicated upon the results of the current Phase III trials. If any of these studies are positive, this compound will likely receive regulatory approval in the USA as well as in any remaining regions of the world where it is currently not approved in recurrent ovarian cancer. The need for central access for administration as well as the schedule disparity between the sarcoma indication (24-hour infusion) versus ovarian cancer (3-hour administration) requires further clarity. Availability of novel effective compounds expands the choices of therapy for patients afflicted with ovarian cancer.