- Email: [email protected]
Clinical development of chemotherapy for uterine leiomyosarcoma
Annals of Oncology 30 (Supplement 6): vi50, 2019 doi:10.1093/annonc/mdz340
PANEL DISCUSSION 4 : CHEMOTHERAPY FOR RARE GYNECOLOGICAL MALIGNANICES 1
Systemic (chemo)therapies for Rare Gynecological Malignancies
Isabelle Ray-Coquard Centre Leon Berard and University Claude Bernard Lyon, France Rare gynecological cancers included real heterogeneous groups of disease and are associated with both difficult challenges and wonderful opportunities. Over the past decade or so, we have made progress in this area through refinement of pathological criteria, hypothesis-generating observational studies, revisiting the indication of adjuvant chemotherapy, and, most importantly, enhanced understanding of the molecular characteristics of several of these subtypes facilitated by technological advances. Surgery remains the cornerstone of management for all subtypes. However, with the exception of malignant ovarian germ cell tumors, for which conventional chemotherapy has been extremely effective, all of the other subtypes discussed herein share the feature of relative insensitivity to standard systemic treatment. Thus, investigation into novel therapeutics is a priority. In France thanks to the GINECO group and the National Cancer Institut (Inca) developed a national network dedicated to rare Gyn cancer since 2010, we have took this opportunity to work within the GCIG network to develop clinical trials dedicated to rare Gyn cancers, to delineate international guidelines. Over the next decade, further progress will occur through a multi-pronged strategy, including welldesigned preclinical investigations, elegant observational and database studies, registries, and innovative clinical trials conducted by national and international networks or consortia as umbrella trials dedicated to Gyn tumors drive by molecular abnormalities.
PD4
2
Novel Targeted Therapies in Uterine Carcinosarcomas
Shin Nishio Department of Obstetrics and Gynecology, Kurume University
recurrence is extremely common (50-80%). UCSs are also aggressive tumors previously considered to be sarcomas, but now recognized as malignancies composed of metaplastic transformation of epithelial elements. Much of the management for UCS has been extrapolated from studies of endometrial carcinomas and sarcomas. The development of novel, effective treatment strategies against UCSs of the female genital tract remains an unmet medical need. Whole exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in UCSs including HER2 (Human Epidermal Growth Factor Receptor 2), PI3K (phosphatidylinositol-3 kinase)/ AKT/mTOR (mammallian target of rapamycin), EGFR (Epidermal Growth Factor Receptor), MARK (mitogen-activated protein kinase), genes related to histones and chromatin structure, and genes related to cell-cycle regulation. The carcinomatous component of these biphasic tumors is suggested to be the catalyst in UCSs tumorigenesis. New strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. This session reviews the genetic landscapes and explores novel targeted treatment modalities against this deadly gynecologic tumor.
PD4
4
Clinical development of chemotherapy for uterine leiomyosarcoma
Tadaaki Nishikawa Department of Breast and Medical Oncology, National Cancer Center Hospital Uterine leiomyosarcoma (uLMS) has a poor prognosis, but the chemotherapy options are still limited due to its rarity. On the other hand, the history of chemotherapy development for uLMS includes two aspects, one is initiated by Gynecologic Clinical Trial Groups, and the other one is studied by trials for soft tissue sarcomas including uLMS. In this session, we would like to discuss the biological differences between uLMS and non-uLMS focusing on the therapeutic target molecules, and also discuss the way of clinical development of chemotherapy for uLMS.
Uterine Carcinosarcomas (UCSs) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for UCSs, the overall five-year survival rate is 30% and
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz340.002/5582785 by University of Cambridge user on 06 November 2019
PD4
PANEL DISCUSSION 4 : CHEMOTHERAPY FOR RARE GYNECOLOGICAL MALIGNANICES 1
Systemic (chemo)therapies for Rare Gynecological Malignancies
Isabelle Ray-Coquard Centre Leon Berard and University Claude Bernard Lyon, France Rare gynecological cancers included real heterogeneous groups of disease and are associated with both difficult challenges and wonderful opportunities. Over the past decade or so, we have made progress in this area through refinement of pathological criteria, hypothesis-generating observational studies, revisiting the indication of adjuvant chemotherapy, and, most importantly, enhanced understanding of the molecular characteristics of several of these subtypes facilitated by technological advances. Surgery remains the cornerstone of management for all subtypes. However, with the exception of malignant ovarian germ cell tumors, for which conventional chemotherapy has been extremely effective, all of the other subtypes discussed herein share the feature of relative insensitivity to standard systemic treatment. Thus, investigation into novel therapeutics is a priority. In France thanks to the GINECO group and the National Cancer Institut (Inca) developed a national network dedicated to rare Gyn cancer since 2010, we have took this opportunity to work within the GCIG network to develop clinical trials dedicated to rare Gyn cancers, to delineate international guidelines. Over the next decade, further progress will occur through a multi-pronged strategy, including welldesigned preclinical investigations, elegant observational and database studies, registries, and innovative clinical trials conducted by national and international networks or consortia as umbrella trials dedicated to Gyn tumors drive by molecular abnormalities.
PD4
2
Novel Targeted Therapies in Uterine Carcinosarcomas
Shin Nishio Department of Obstetrics and Gynecology, Kurume University
recurrence is extremely common (50-80%). UCSs are also aggressive tumors previously considered to be sarcomas, but now recognized as malignancies composed of metaplastic transformation of epithelial elements. Much of the management for UCS has been extrapolated from studies of endometrial carcinomas and sarcomas. The development of novel, effective treatment strategies against UCSs of the female genital tract remains an unmet medical need. Whole exome sequencing studies have recently demonstrated mutations or aberrant activation of multiple genes/pathways in UCSs including HER2 (Human Epidermal Growth Factor Receptor 2), PI3K (phosphatidylinositol-3 kinase)/ AKT/mTOR (mammallian target of rapamycin), EGFR (Epidermal Growth Factor Receptor), MARK (mitogen-activated protein kinase), genes related to histones and chromatin structure, and genes related to cell-cycle regulation. The carcinomatous component of these biphasic tumors is suggested to be the catalyst in UCSs tumorigenesis. New strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. This session reviews the genetic landscapes and explores novel targeted treatment modalities against this deadly gynecologic tumor.
PD4
4
Clinical development of chemotherapy for uterine leiomyosarcoma
Tadaaki Nishikawa Department of Breast and Medical Oncology, National Cancer Center Hospital Uterine leiomyosarcoma (uLMS) has a poor prognosis, but the chemotherapy options are still limited due to its rarity. On the other hand, the history of chemotherapy development for uLMS includes two aspects, one is initiated by Gynecologic Clinical Trial Groups, and the other one is studied by trials for soft tissue sarcomas including uLMS. In this session, we would like to discuss the biological differences between uLMS and non-uLMS focusing on the therapeutic target molecules, and also discuss the way of clinical development of chemotherapy for uLMS.
Uterine Carcinosarcomas (UCSs) in gynecology are very infrequent and represent only 2-5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for UCSs, the overall five-year survival rate is 30% and
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz340.002/5582785 by University of Cambridge user on 06 November 2019
PD4