Jacek P Grabowski1, Philipp Harter2, Florian Heitz2, Eric Pujade-Lauraine3, Alexander Reuss4, Gunnar Kristensen5, Isabelle Ray-Coquard6, Julia Heitz7, Alexander Traut2, Jacobus Pfisterer8, Andreas du Bois2. 1. Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany; Department of Gynecology, European Competence Center for Ovarian Cancer, Charite-University Medicine of Berlin, Augustenberger Platz 1, 13353 Berlin, Germany. Electronic address: jacgrab@yahoo.com. 2. Department of Gynecology and Gynecological Oncology, Kliniken Essen Mitte, Henricistrasse 92, 45136 Essen, Germany. 3. Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Oncology Department, Universite Paris Descartes, AP-HP, Hopitaux Universitaires Paris Centre, Site Hotel Dieu, Paris, France. 4. Koordinierungszentrum fuer Klinische Studien, Philipps-Universitaet Marburg, Karl-von-Frisch-Str. 4, 35043 Marburg, Germany. 5. Nordic Society of Gynaecological Oncology Group (NSGO), Department of Gynecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, PB4953 Nydalen, 0424 Oslo, Norway. 6. Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Université de Lyon-Centre Léon Bérard, Department of Medical Oncology and EA SIS, 4128 Lyon, France. 7. Department of Gynecology and Obstetrics, Klinikum Duisburg, Zu den Rehwiesen 9-11, 47055 Duisburg, Germany. 8. Gynecologic Oncology Center, Kiel, Herzog-Friedrich-Str. 21, 24103 Kiel, Germany.
Abstract
OBJECTIVE: Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. METHODS: This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. RESULTS: Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). CONCLUSIONS: Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations.
OBJECTIVE: Since almost two decades standard 1st-line chemotherapy for advanced ovarian cancer (AOC) has been a platinum/taxane combination. More recently, this general strategy has been challenged because different types of AOC may not benefit homogenously. Low-grade serous ovarian cancer (LGSOC) is one of the candidates in whom efficacy of standard chemotherapy should be revised. METHODS: This study is an exploratory case control study of the AGO-metadatabase of 4 randomized phase III trials with first-line platinum combination chemotherapy without any targeted therapy. Patients with advanced FIGO IIIBIV low-grade serous ovarian cancer were included and compared with control cases having high-grade serous AOC. RESULTS: Out of 5114 patients in this AGO database 145 (2.8%) had LGSOC and of those thirty-nine (24.1%) had suboptimal debulking with post-operative residual tumor >1cm, thus being eligible for response evaluation. An objective response was observed in only 10 patients and this 23.1% response rate (RR) was significantly lower compared to 90.1% RR in the control cohort of high-grade serous ovarian cancer (HGSOC) (p<0.001). Both, LGSOC and HGSOC patients who underwent complete cytoreduction had significantly better progression free survival (PFS) and overall survival (OS) in comparison to those with residuals after primary surgery, accordingly (p<0.001). CONCLUSIONS: Our observation indicates that low-grade serous cancer is not as responsive to platinum-taxane-based chemotherapy as high-grade serous AOC. In contrast, surgical debulking showed a similar impact on outcome in both types of AOC thus indicating different roles for both standard treatment modalities. Systemic treatment of low grade serous AOC urgently warrants further investigations.
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