Phase III trial comparing adjuvant treatment with pegylated interferon alfa-2b versus observation

Prognostic significance of autoantibodies - EORTC 18991

Marna G. Bouwhuis, Stefan Suciu, Alessandro Testori, Wim H. Kruit, François Salès, Poulam Patel, Cornelis J. Punt, Mario Santinami, Alain Spatz, Timo L M Ten Hagen, Alexander M M Eggermont

Research output: Contribution to journalArticle

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Abstract

Purpose: Conflicting data have been reported concerning the prognostic value of autoimmune antibodies in patients with melanoma treated with adjuvant interferon alfa-2b (IFN). We evaluated the prognostic significance of autoantibodies in the European Organisation for Research and Treatment of Cancer 18991 trial, comparing long-term administration of pegylated IFN (PEG-IFN) with observation. Patients and Methods: Anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined by enzyme-linked immunosorbent assays in 296 patients before random assignment and every 6 months after random assignment for up to 5 years. Prognostic impact of autoantibodies on recurrence-free survival (RFS) was assessed using the following three Cox models: a model that considered autoantibody appearance as a time-independent variable (model 1); a model that considered a patient to be autoantibody positive from the first positive test (model 2); and a model in which the most recent autoantibody test was used to define the status of the patient (model 3). Results: Patients who were autoantibody negative at baseline were analyzed (n = 220). Occurrence of autoantibodies during follow-up was higher in the PEG-IFN-treated patients (18% in the observation arm v 52% in the PEG-IFN arm). Autoantibody appearance was of prognostic importance by using model 1 (hazard ratio [HR] = 0.56; 95% CI, 0.36 to 0.87; P = .01). However, when guarantee-time bias was taken into account using model 2 (HR = 1.19; 95% CI, 0.75 to 1.88; P = .46) or method 3 (HR = 1.14; 95% CI, 0.71 to 1.83; P = .59), significance was lost. Results were similar when treatment groups were analyzed separately. Conclusion: Appearance of autoimmune antibodies is neither a prognostic nor a predictive factor for improved outcome in patients with melanoma treated with PEG-IFN.

Original languageEnglish
Pages (from-to)2460-2466
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number14
DOIs
Publication statusPublished - May 10 2010

Fingerprint

Autoantibodies
Observation
Proportional Hazards Models
interferon alfa-2b
Therapeutics
Melanoma
Anticardiolipin Antibodies
peginterferon alfa-2b
Antibodies
Antinuclear Antibodies
Enzyme-Linked Immunosorbent Assay
Recurrence
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase III trial comparing adjuvant treatment with pegylated interferon alfa-2b versus observation : Prognostic significance of autoantibodies - EORTC 18991. / Bouwhuis, Marna G.; Suciu, Stefan; Testori, Alessandro; Kruit, Wim H.; Salès, François; Patel, Poulam; Punt, Cornelis J.; Santinami, Mario; Spatz, Alain; Ten Hagen, Timo L M; Eggermont, Alexander M M.

In: Journal of Clinical Oncology, Vol. 28, No. 14, 10.05.2010, p. 2460-2466.

Research output: Contribution to journalArticle

Bouwhuis, MG, Suciu, S, Testori, A, Kruit, WH, Salès, F, Patel, P, Punt, CJ, Santinami, M, Spatz, A, Ten Hagen, TLM & Eggermont, AMM 2010, 'Phase III trial comparing adjuvant treatment with pegylated interferon alfa-2b versus observation: Prognostic significance of autoantibodies - EORTC 18991', Journal of Clinical Oncology, vol. 28, no. 14, pp. 2460-2466. https://doi.org/10.1200/JCO.2009.24.6264
Bouwhuis, Marna G. ; Suciu, Stefan ; Testori, Alessandro ; Kruit, Wim H. ; Salès, François ; Patel, Poulam ; Punt, Cornelis J. ; Santinami, Mario ; Spatz, Alain ; Ten Hagen, Timo L M ; Eggermont, Alexander M M. / Phase III trial comparing adjuvant treatment with pegylated interferon alfa-2b versus observation : Prognostic significance of autoantibodies - EORTC 18991. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 14. pp. 2460-2466.
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abstract = "Purpose: Conflicting data have been reported concerning the prognostic value of autoimmune antibodies in patients with melanoma treated with adjuvant interferon alfa-2b (IFN). We evaluated the prognostic significance of autoantibodies in the European Organisation for Research and Treatment of Cancer 18991 trial, comparing long-term administration of pegylated IFN (PEG-IFN) with observation. Patients and Methods: Anticardiolipin, antithyroglobulin, and antinuclear antibodies were determined by enzyme-linked immunosorbent assays in 296 patients before random assignment and every 6 months after random assignment for up to 5 years. Prognostic impact of autoantibodies on recurrence-free survival (RFS) was assessed using the following three Cox models: a model that considered autoantibody appearance as a time-independent variable (model 1); a model that considered a patient to be autoantibody positive from the first positive test (model 2); and a model in which the most recent autoantibody test was used to define the status of the patient (model 3). Results: Patients who were autoantibody negative at baseline were analyzed (n = 220). Occurrence of autoantibodies during follow-up was higher in the PEG-IFN-treated patients (18{\%} in the observation arm v 52{\%} in the PEG-IFN arm). Autoantibody appearance was of prognostic importance by using model 1 (hazard ratio [HR] = 0.56; 95{\%} CI, 0.36 to 0.87; P = .01). However, when guarantee-time bias was taken into account using model 2 (HR = 1.19; 95{\%} CI, 0.75 to 1.88; P = .46) or method 3 (HR = 1.14; 95{\%} CI, 0.71 to 1.83; P = .59), significance was lost. Results were similar when treatment groups were analyzed separately. Conclusion: Appearance of autoimmune antibodies is neither a prognostic nor a predictive factor for improved outcome in patients with melanoma treated with PEG-IFN.",
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AU - Suciu, Stefan

AU - Testori, Alessandro

AU - Kruit, Wim H.

AU - Salès, François

AU - Patel, Poulam

AU - Punt, Cornelis J.

AU - Santinami, Mario

AU - Spatz, Alain

AU - Ten Hagen, Timo L M

AU - Eggermont, Alexander M M

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