Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials

A. Le Cesne, M. Ouali, M. G. Leahy, A. Santoro, H. J. Hoekstra, P. Hohenberger, F. Van Coevorden, P. Rutkowski, R. Van Hoesel, J. Verweij, S. Bonvalot, W. P. Steward, A. Gronchi, P. C W Hogendoorn, S. Litiere, S. Marreaud, J. Y. Blay, W. T A Van Der Graaf

Research output: Contribution to journalArticle

Abstract

BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.

PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor.

RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients

CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

Original languageEnglish
Pages (from-to)2425-2432
Number of pages8
JournalAnnals of Oncology
Volume25
Issue number12
DOIs
Publication statusPublished - Dec 1 2014

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Phase III Clinical Trials
Adjuvant Chemotherapy
Sarcoma
Doxorubicin
Survival
Recurrence
Standard of Care
Multivariate Analysis
Observation
Pathology
Drug Therapy

Keywords

  • adjuvant chemotherapy
  • predictive factors
  • soft tissue sarcoma
  • treatment outcome

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Le Cesne, A., Ouali, M., Leahy, M. G., Santoro, A., Hoekstra, H. J., Hohenberger, P., ... Van Der Graaf, W. T. A. (2014). Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials. Annals of Oncology, 25(12), 2425-2432. https://doi.org/10.1093/annonc/mdu460

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma : pooled analysis of two STBSG-EORTC phase III clinical trials. / Le Cesne, A.; Ouali, M.; Leahy, M. G.; Santoro, A.; Hoekstra, H. J.; Hohenberger, P.; Van Coevorden, F.; Rutkowski, P.; Van Hoesel, R.; Verweij, J.; Bonvalot, S.; Steward, W. P.; Gronchi, A.; Hogendoorn, P. C W; Litiere, S.; Marreaud, S.; Blay, J. Y.; Van Der Graaf, W. T A.

In: Annals of Oncology, Vol. 25, No. 12, 01.12.2014, p. 2425-2432.

Research output: Contribution to journalArticle

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, PCW, Litiere, S, Marreaud, S, Blay, JY & Van Der Graaf, WTA 2014, 'Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials', Annals of Oncology, vol. 25, no. 12, pp. 2425-2432. https://doi.org/10.1093/annonc/mdu460
Le Cesne, A. ; Ouali, M. ; Leahy, M. G. ; Santoro, A. ; Hoekstra, H. J. ; Hohenberger, P. ; Van Coevorden, F. ; Rutkowski, P. ; Van Hoesel, R. ; Verweij, J. ; Bonvalot, S. ; Steward, W. P. ; Gronchi, A. ; Hogendoorn, P. C W ; Litiere, S. ; Marreaud, S. ; Blay, J. Y. ; Van Der Graaf, W. T A. / Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma : pooled analysis of two STBSG-EORTC phase III clinical trials. In: Annals of Oncology. 2014 ; Vol. 25, No. 12. pp. 2425-2432.
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AU - Leahy, M. G.

AU - Santoro, A.

AU - Hoekstra, H. J.

AU - Hohenberger, P.

AU - Van Coevorden, F.

AU - Rutkowski, P.

AU - Van Hoesel, R.

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AU - Bonvalot, S.

AU - Steward, W. P.

AU - Gronchi, A.

AU - Hogendoorn, P. C W

AU - Litiere, S.

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AU - Blay, J. Y.

AU - Van Der Graaf, W. T A

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N2 - BACKGROUND: The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.PATIENTS AND METHODS: Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor.RESULTS: A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients CONCLUSION: Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.

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