Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Prospective, Multicenter, Phase IV Trial

被引：5

作者：

Gruenwald, Viktor ^{[1
,2
]}

Pink, Daniel ^{[3
,4
]}

Egerer, Gerlinde ^{[5
]}

Schalk, Enrico ^{[6
]}

Augustin, Marinela ^{[7
]}

Deinzer, Christoph K. W. ^{[8
]}

Kob, Viola ^{[9
]}

Reichert, Dietmar ^{[10
]}

Kebenko, Maxim ^{[11
]}

Brandl, Stephan ^{[12
]}

Hahn, Dennis ^{[13
]}

Lindner, Lars H. ^{[14
]}

Hoiczyk, Mathias ^{[15
]}

Ringsdorf, Uta ^{[16
]}

Hanker, Lars C. ^{[17
]}

Hempel, Dirk ^{[18
]}

De Rivas, Beatriz ^{[19
]}

Wismann, Tobias ^{[20
]}

Ivanyi, Philipp ^{[21
]}

机构：

[1] Univ Klinikum Essen, Innere Klin Tumorforsch, D-45147 Essen, Germany

[2] Univ Klinikum Essen, Klin Urol, D-45147 Essen, Germany

[3] Sarkomzentrum Berlin Brandenburg, Klin Onkol & Palliat Med, Helios Klinikum Bad Saarow, D-15526 Bad Saarow Pieskow, Germany

[4] Univ Med Greifswald, Innere Med C, D-17489 Greifswald, Germany

[5] Univ Klinikum Heidelberg, Klin Hamatol Onkol Rheumatol, D-69120 Heidelberg, Germany

[6] Otto von Guericke Univ, Med Ctr, D-39106 Magdeburg, Germany

[7] Paracelsus Med Privatuniv, Klin Innere Med 5, Schwerpunkt Onkol Hamatol, Klinikum Nurnberg Nord, D-90419 Nurnberg, Germany

[8] Univ Klinikum Wurzburg, Med Klin & Poliklin 2, Hamatol & Internist Onkol, D-97078 Wurzburg, Germany

[9] MVZ Immunol Lokstedt GmbH, Schwerpunktpraxis Hamatol Onkol Volksdorf, D-20251 Hamburg, Germany

[10] Gemeinschaftspraxis Hamatol & Onkol, Kuhlenstr 53d, D-26655 Westerstede, Germany

[11] Univ Klinikum Schleswig Holstein, Klin Hamatol & Onkol, D-23538 Lubeck, Germany

[12] Uberortl Gemeinschaftspraxis Bergedorf, D-21029 Hamburg, Germany

[13] Klinikum Stuttgart, Klin Hamatol Onkol & Palliat Med, D-70174 Stuttgart, Germany

[14] LMU Klinikum, Med Klin & Poliklin 3, Campus Grosshadern, D-81377 Munich, Germany

[15] Marien Hosp Wesel gGmbH, Med Klin 2, D-46483 Wesel, Germany

[16] Lahn Dill Kliniken GmbH, Gynakol Tumorzentrums Lahn Dill, D-35578 Wetzlar, Germany

[17] Univ Klinikum Schleswig Holstein, Klin Frauenheilkunde & Geburtshilfe Gynakol, D-23538 Lubeck, Germany

[18] Onkol Zentrum, D-86609 Donauworth, Germany

[19] PharmaMar SA, Med Affairs, Madrid 28770, Spain

[20] Praxis Onkol & Urol, D-26389 Wilhelmshaven, Germany

[21] Hannover Med Sch, Claudia von Schilling Zentrum, Hamostaseol Onkol & Stammzelltransplantat, Klin Hamatol,Comprehens Canc Ctr, D-30625 Hannover, Germany

来源：

CANCERS | 2022年 / 14卷 / 21期

关键词：

trabectedin; STS; sarcoma; non-interventional; prospective; CLINICAL-PRACTICE GUIDELINES; METASTATIC LIPOSARCOMA; SUPPORTIVE CARE; CHEMOTHERAPY; MECHANISM; EFFICACY; SAFETY; LEIOMYOSARCOMA; DIAGNOSIS; FAILURE;

D O I：

10.3390/cancers14215234

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This non-interventional, prospective phase IV trial evaluated trabectedin in patients with soft tissue sarcoma (STS) in real-life clinical practice across Germany. The primary endpoints were progression-free survival (PFS) rates at 3 and 6 months, as defined by investigators. Overall, 128 patients from 19 German sites were evaluated for efficacy and 130 for safety. Median age was 58.5 years (range: 23-84) and leiomyosarcoma was the most frequent histotype (n = 45; 35.2%). Trabectedin was mostly used as second/third-line treatment (n = 91; 71.1%). Median PFS was 5.2 months (95% CI: 3.3-6.7), with 60.7% and 44.5% of patients free from progression at 3 and 6 months, respectively. Median overall survival was 15.2 months (95% CI: 9.6-21.4). One patient achieved a complete and 14 patients a partial response, conferring an objective response rate of 11.7%. Decreases in white blood cells (27.0% of patients), platelets (16.2%) and neutrophils (13.1%) and increased alanine aminotransferase (10.8%) were the most common trabectedin-related grade 3/4 adverse drug reactions. Two deaths due to pneumonia and sepsis were considered trabectedin-related. Trabectedin confers clinically meaningful activity in patients with multiple STS histotypes, comparable to that previously observed in clinical trials and other non-interventional studies, and with a manageable safety profile.

引用

页数：15

共 32 条

[1]

[Anonymous], YONDELIS SUMMARY PRO

[2] Long-term outcome and effect of maintenance therapy in patients with advanced sarcoma treated with trabectedin: an analysis of 181 patients of the French ATU compassionate use program [J].

Blay, Jean-Yves ;

Italiano, Antoine ;

Ray-Coquard, Isabelle ;

Le Cesne, Axel ;

Duffaud, Florence ;

Rios, Maria ;

Collard, Olivier ;

Bertucci, Francois ;

Bompas, Emmanuelle ;

Isambert, Nicolas ;

Chaigneau, Loic ;

Cassier, Philippe ;

Bui, Binh ;

Decanter, Gauthier ;

Derbel, Olfa ;

Coindre, Jean-Michel ;

Zintl, Patrick ;

Badri, Nadia ;

Penel, Nicolas .

BMC CANCER, 2013, 13

[3] A noninterventional, multicenter, prospective phase IV study of trabectedin in patients with advanced soft tissue sarcoma [J].

Buonadonna, Angela ;

Benson, Charlotte ;

Casanova, Jose ;

Kasper, Bernd ;

Lopez Pousa, Antonio ;

Mazzeo, Filomena ;

Brodowicz, Thomas ;

Penel, Nicolas .

ANTI-CANCER DRUGS, 2017, 28 (10) :1157-1165

[4] The Epidemiology of Sarcoma [J].

Burningham, Zachary ;

Hashibe, Mia ;

Spector, Logan ;

Schiffman, Joshua D. .

CLINICAL SARCOMA RESEARCH, 2012, 2

[5] Soft tissue and visceral sarcomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up (vol 29, pg 51, 2018) [J].

Casali, P. G. ;

Abecassis, N. ;

Aro, H. T. ;

Bauer, S. ;

Biagini, R. ;

Bielack, S. ;

Bonvalot, S. ;

Boukovinas, I. ;

Bovee, J. V. M. G. ;

Brodovvicz, T. ;

Broto, J. M. ;

Buonadonna, A. ;

De Alava, E. ;

Tos, A. P. Dei ;

Del Muro, X. G. ;

Dileo, P. ;

Eriksson, M. ;

Fedenko, A. ;

Ferraresi, V. ;

Ferrari, A. ;

Ferrari, S. ;

Frezza, A. M. ;

Gasperoni, S. ;

Gelderblom, H. ;

Gil, T. ;

Grignani, G. ;

Gronchi, A. ;

Haas, R. L. ;

Hassan, B. ;

Hohenberger, P. ;

Lssels, R. ;

Joensuu, H. ;

Jones, R. L. ;

Judson, I. ;

Jutte, P. ;

Kaal, S. ;

Kasper, B. ;

Kopeckova, K. ;

Krakorova, D. A. ;

Le Cesne, A. ;

Lugowska, I. ;

Merimsky, O. ;

Montemurro, M. ;

Pantaleo, M. A. ;

Piana, R. ;

Picci, P. ;

Piperno-Neumann, S. ;

Pousa, A. L. ;

Reichardt, P. ;

Robinson, M. H. .

ANNALS OF ONCOLOGY, 2018, 29 :268-269

[6] Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].

Casali, Paolo G. ;

Blay, Jean-Yves ;

Bertuzzi, Alexia ;

Bielack, Stefan ;

Bjerkehagen, Bodil ;

Bonvalot, Sylvie ;

Boukovinas, Ioannis ;

Bruzzi, Paolo ;

Dei Tos, Angelo Paolo ;

Dileo, Palma ;

Eriksson, Mikael ;

Fedenko, Alexander ;

Ferrari, Andrea ;

Ferrari, Stefano ;

Gelderblom, Hans ;

Grimer, Robert ;

Gronchi, Alessandro ;

Haas, Rick ;

Hall, Kirsten Sundby ;

Hohenberger, Peter ;

Issels, Rolf ;

Joensuu, Heikki ;

Judson, Ian ;

Le Cesne, Axel ;

Litiere, Saskia ;

Martin-Broto, Javier ;

Merimsky, Ofer ;

Montemurro, Michael ;

Morosi, Carlo ;

Picci, Piero ;

Ray-Coquard, Isabelle ;

Reichardt, Peter ;

Rutkowski, Piotr ;

Schlemmer, Marcus ;

Stacchiotti, Silvia ;

Torri, Valter ;

Trama, Annalisa ;

Van Coevorden, Frits ;

Van der Graaf, Winette ;

Vanel, Daniel ;

Wardelmann, Eva .

ANNALS OF ONCOLOGY, 2014, 25 :102-112

[7] Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: Proposal of new computed tomography response criteria [J].

Choi, Haesun ;

Charnsangavej, Chuslip ;

Faria, Silvana C. ;

Macapinlac, Homer A. ;

Burgess, Michael A. ;

Patel, Shreyaskumar R. ;

Chen, Lei L. ;

Podoloff, Donald A. ;

Benjamin, Robert S. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (13) :1753-1759

[8] Trabectedin mechanism of action: what's new? [J].

D'Incalci, Maurizio .

FUTURE ONCOLOGY, 2013, 9 (12) :5-10

[9] A Review of Trabectedin (ET-743): A Unique Mechanism of Action [J].

D'Incalci, Maurizio ;

Galmarini, Carlos M. .

MOLECULAR CANCER THERAPEUTICS, 2010, 9 (08) :2157-2163

[10] Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma [J].

De Sanctis, Rita ;

Marrari, Andrea ;

Marchetti, Silvia ;

Mussi, Chiara ;

Balzarini, Luca ;

Lutman, Fabio Romano ;

Daolio, Primo ;

Bastoni, Stefano ;

Bertuzzi, Alexia Francesca ;

Quagliuolo, Vittorio ;

Santoro, Armando .

DRUG DESIGN DEVELOPMENT AND THERAPY, 2015, 9 :5785-5791

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