Hopes and failures in front-line ovarian cancer therapy

https://doi.org/10.1016/j.critrevonc.2019.08.002Get rights and content
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Abstract

Through the last three decades, the combination of paclitaxel and carboplatin remains the standard of care chemotherapy in newly diagnosed epithelial ovarian cancer (EOC). Based on a single trial, first-line maintenance therapy with angiogenesis inhibitor bevacizumab was approved in Europe and widely applied. In 2018, based on a second trial bevacizumab was approved for first-line maintenance in the United States. Despite complete remission upon chemotherapy, the majority of the patients recur. A large number of randomized trials were conducted to explore the optimal front-line therapy regimen, but neither dose-densing, nor adding of a third chemotherapy agent or intraperitoneal administration could improve overall survival (OS). Also implementation of hyperthermic intraperitoneal chemotherapy (HIPEC) or the neoadjuvant approach failed to improve OS.

Recently, maintenance therapy with PARP inhibitors showed encouraging results in patients with BRCA1/2 mutation. Further trials with targeted therapies are ongoing.

Here we review the achievements of front-line therapy in primary advanced EOC through the last three decades and discuss future treatment strategies.

Keywords

Ovarian cancer
Front-line therapy
Overall survival
Systemic therapy
Maintenance

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Irina Tsibulak was born in Ukraine and graduated in Medicine at the Medical University of Innsbruck, Austria, in 2015. In 2015–2016 she was a surgical resident at the Department of Visceral, Transplant and Thoracic Surgery in Innsbruck. From 2016 she is a resident doctor at the Department of Obstetrics and Gynecology of Innsbruck University Hospital and is involved in clinical research on gynecologic oncology.

Alain G. Zeimet was born in Luxembourg and graduated in Medicine at the University of Innsbruck, Austria, in 1990. From 1988–1989 he was a scientific fellow of Prof. P.M. Martin, University of Aix-en-Provence/Marseille; Institute of Experimental Cancer Research, Department of Steroid Receptor Research (CRNS-Unit), Marseille. He completed his Obstetrics and Gynecology residency at the Department of Obstetrics and Gynecology of Innsbruck University Hospital in 1997 and he qualified as professor in 1998 (PhD). Since 2002 Dr. Zeimet is the Vice Head of the Department of Obstetrics and Gynecology and the Head of the Gynecologic Oncology unit at the Medical University of Innsbruck. His clinical and research interests focus the field of ovarian and endometrial cancer. Dr. Zeimet authored more than 180 scientific research articles. He was the president of the Austrian Association for Gynecologic Oncology from 2005 to 2007 and in a second term from 2013 – 2015. He is a member of numerous national and international scientific organizations and guidelines committees for gynecologic cancers.

Christian Marth is Head and Professor of the Department of Obstetrics and Gynecology at Innsbruck Medical University in Austria. After graduating in medicine from Innsbruck Medical University in 1985, he specialized in obstetrics and gynecology in Innsbruck, becoming senior physician in 1990. A year later he became a specialist in obstetrics and gynaecology, and completed his habilitation. In 1996, Christian Marth moved to The Norwegian Radiumhospital, Oslo, where he was senior physician at the Department of Gynecologic Oncology. After being made Associate Professor at the University of Innsbruck in 1997, he returned to Innsbruck in 1998 as Head of the Department of Obstetrics and Gynecology. Christian Marth has been President of the Austrian Association for Gynecologic Oncology (2001–2003, 2013–2016), Chair of the Ovarian Committee of Gynecological Cancer Intergroup (2007–2012), a Council member of the European Society of Gynecologic Oncology ESGO (2009–2016), President of the Austrian Association of Obstetrics and Gynecology (2011–2013), and Chair of the European Network of Gynaecological Oncological Trial Groups (2014–2016). Currently, he is the President of the Austrian Study Center for Gynecologic Oncology (since 2002), and Vice-President of the Austrian Breast and Colorectal Study Group (since 2006). Christian Marth has also been the author or co-author of more than 400 peer-reviewed scientific articles, and has received 13 national and international awards.