Soft tissue sarcoma - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main STS page for regimens that include active anticancer treatment.
=Neoadjuvant therapy=
==No neoadjuvant therapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Awaiting publication (STRASS2)	2020-2027 	Phase 3 (C)	1a. AI1b. EI	TBD if different primary endpoint of DFS
No systemic anticancer treatment before surgery.
====Subsequent treatment====
*Surgery
===References===
#STRASS2: NCT04031677
=Adjuvant therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bramwell et al. 1994 (EORTC 62771)	1977-1988 	Phase 3 (C)	CYVADIC 	Shorter RFS
Woll et al. 2012 (EORTC 62931) 	1995-2003 	Phase 3 (C)	AI 	Did not meet primary endpoint of OS
Gronchi et al. 2012 	2002-2007 	Phase 3 (C)	EI 	Non-inferior OS
No further treatment.
====Preceding treatment====
*Gronchi et al. 2012: Neoadjuvant EI x 3, then surgery
*EORTC 62931: Surgery +/- RT
===References===
# EORTC 62771: Bramwell V, Rouesse J, Steward W, Santoro A, Schraffordt-Koops H, Buesa J, Ruka W, Priario J, Wagener T, Burgers M, Van Unnik J, Contesso G, Thomas D, Van Glabbeke M, Markham D, Pinedo H. Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. J Clin Oncol. 1994 Jun;12(6):1137-49. link to original article EuroPMC
## Pooled update: Le Cesne A, Ouali M, Leahy MG, Santoro A, Hoekstra HJ, Hohenberger P, Van Coevorden F, Rutkowski P, Van Hoesel R, Verweij J, Bonvalot S, Steward WP, Gronchi A, Hogendoorn PC, Litiere S, Marreaud S, Blay JY, Van Der Graaf WT. Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials. Ann Oncol. 2014 Dec;25(12):2425-32. Epub 2014 Oct 6. link to original article EuroPMC
# Gronchi A, Frustaci S, Mercuri M, Martin J, Lopez-Pousa A, Verderio P, Mariani L, Valagussa P, Miceli R, Stacchiotti S, Dei Tos AP, De Paoli A, Longhi A, Poveda A, Quagliuolo V, Comandone A, Casali PG, Picci P; Italian Sarcoma Group; Spanish Sarcoma Group. Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group. J Clin Oncol. 2012 Mar 10;30(8):850-6. Epub 2012 Feb 6. link to original article EuroPMC EudraCT 2004-003979-36
# EORTC 62931: Woll PJ, Reichardt P, Le Cesne A, Bonvalot S, Azzarelli A, Hoekstra HJ, Leahy M, Van Coevorden F, Verweij J, Hogendoorn PC, Ouali M, Marreaud S, Bramwell VH, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; NCIC Clinical Trials Group Sarcoma Disease Site Committee. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol. 2012 Oct;13(10):1045-54. Epub 2012 Sep 4. link to original article EuroPMC NCT00002641
## Pooled update: Le Cesne A, Ouali M, Leahy MG, Santoro A, Hoekstra HJ, Hohenberger P, Van Coevorden F, Rutkowski P, Van Hoesel R, Verweij J, Bonvalot S, Steward WP, Gronchi A, Hogendoorn PC, Litiere S, Marreaud S, Blay JY, Van Der Graaf WT. Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials. Ann Oncol. 2014 Dec;25(12):2425-32. Epub 2014 Oct 6. link to original article EuroPMC
=Locally advanced or metastatic disease=
==Best supportive care==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Le Cesne et al. 2021 (T-SAR)	2015-01-26 to 2015-11-05	Phase 3 (C)	Trabectedin	Shorter PFSMedian PFS: 1.5 vs 3.1 mo(HR 2.56, 95% CI 1.56-4.17)
No antineoplastic treatment.
===References===
# T-SAR: Le Cesne A, Blay JY, Cupissol D, Italiano A, Delcambre C, Penel N, Isambert N, Chevreau C, Bompas E, Bertucci F, Chaigneau L, Piperno-Neumann S, Salas S, Rios M, Guillemet C, Bay JO, Ray-Coquard I, Haddag L, Bonastre J, Kapso R, Fraslin A, Bouvet N, Mir O, Foulon S. A randomized phase III trial comparing trabectedin to best supportive care in patients with pre-treated soft tissue sarcoma: T-SAR, a French Sarcoma Group trial. Ann Oncol. 2021 Aug;32(8):1034-1044. Epub 2021 Apr 29. link to original article EuroPMC NCT02672527
==Placebo==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Demetri et al. 2013 (SUCCEED) 	2007-2010 	Phase 3 (C) 	Ridaforolimus	Shorter PFS (primary endpoint)Median PFS: 14.6 vs 17.7 weeks(HR 1.39, 95% CI 1.18-1.64)
van der Graaf et al. 2012 (PALETTE)	2008-2010 	Phase 3 (C) 	Pazopanib 	Shorter PFSMedian PFS: 1.6 vs 4.6 mo(HR 3.23, 95% CI 2.50-4.17)
Kawai et al. 2015 	2012-2014 	Randomized Phase 2 (C)	Trabectedin 	Shorter PFSMedian PFS: 0.9 vs 5.6 mo(HR 14.29, 95% CI 6.25-33.33)
Mir et al. 2016 (REGOSARC) 	2013-08-05 to 2014-11-26	Randomized Phase 2 (C)	Regorafenib 	Shorter PFS1
1Reported efficacy in REGOSARC is for the leiomyosarcoma, synovial sarcoma, and other sarcoma cohorts; there was no significant difference in outcome for the liposarcoma cohort.
No active antineoplastic treatment.
===References===
# PALETTE: van der Graaf WT, Blay JY, Chawla SP, Kim DW, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P; EORTC Soft Tissue and Bone Sarcoma Group; PALETTE study group. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012 May 19;379(9829):1879-86. Epub 2012 May 16. link to original article EuroPMC NCT00753688
##HRQoL analysis: Coens C, van der Graaf WT, Blay JY, Chawla SP, Judson I, Sanfilippo R, Manson SC, Hodge RA, Marreaud S, Prins JB, Lugowska I, Litière S, Bottomley A. Health-related quality-of-life results from PALETTE: A randomized, double-blind, phase 3 trial of pazopanib versus placebo in patients with soft tissue sarcoma whose disease has progressed during or after prior chemotherapy-a European Organization for research and treatment of cancer soft tissue and bone sarcoma group global network study (EORTC 62072). Cancer. 2015 Sep 1;121(17):2933-41. Epub 2015 May 29. link to original article EuroPMC
## Subgroup analysis: Kawai A, Araki N, Hiraga H, Sugiura H, Matsumine A, Ozaki T, Ueda T, Ishii T, Esaki T, Machida M, Fukasawa N. A randomized, double-blind, placebo-controlled, phase III study of pazopanib in patients with soft tissue sarcoma: results from the Japanese subgroup. Jpn J Clin Oncol. 2016 Mar;46(3):248-53. Epub 2016 Feb 10. link to original article link to PMC article EuroPMC
# SUCCEED: Demetri GD, Chawla SP, Ray-Coquard I, Le Cesne A, Staddon AP, Milhem MM, Penel N, Riedel RF, Bui-Nguyen B, Cranmer LD, Reichardt P, Bompas E, Alcindor T, Rushing D, Song Y, Lee RM, Ebbinghaus S, Eid JE, Loewy JW, Haluska FG, Dodion PF, Blay JY. Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J Clin Oncol. 2013 Jul 1;31(19):2485-92. Epub 2013 May 28. link to original article EuroPMC NCT00538239
# Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. Lancet Oncol. 2015 Apr;16(4):406-16. Epub 2015 Mar 18. link to original article EuroPMC JapicCTI-121850
# REGOSARC: Mir O, Brodowicz T, Italiano A, Wallet J, Blay JY, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N. Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1732-1742. Epub 2016 Oct 14. link to original article EuroPMC NCT01900743
Category:Soft tissue sarcoma regimens
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Category:Soft tissue sarcomas
Category:Null regimens