Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial

Alexander M.M. Eggermont, Vanna Chiarion-Sileni, Jean Jacques Grob, Reinhard Dummer, Jedd D. Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo Antonio Ascierto, Jon M. Richards, Celeste Lebbe, Virginia Ferraresi, Michael Smylie, Jeffrey S. Weber, Michele Maio, Fareeda Hosein, Veerle de Pril, Michal Kicinski, Stefan Suciu, Alessandro Testori

Research output: Contribution to journalArticle

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Abstract

Background: Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and results: A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63–0.88; P < 0.001), DMFS (HR: 95% CI: 0.76, 0.64–0.90; P = 0.002) and OS (HR: 0.73, 95% CI: 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups. Conclusions: Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalEuropean Journal of Cancer
Volume119
DOIs
Publication statusPublished - Sep 1 2019

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Melanoma
Placebos
Survival
Neoplasm Metastasis
Recurrence
ipilimumab
Confidence Intervals
Lymph Nodes
Intention to Treat Analysis
Therapeutics
Intravenous Infusions
Research Personnel

Keywords

  • Adjuvant therapy
  • Ipilimumab
  • Long-term results
  • Melanoma
  • Phase III trial
  • Stage III

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma : long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial. / Eggermont, Alexander M.M.; Chiarion-Sileni, Vanna; Grob, Jean Jacques; Dummer, Reinhard; Wolchok, Jedd D.; Schmidt, Henrik; Hamid, Omid; Robert, Caroline; Ascierto, Paolo Antonio; Richards, Jon M.; Lebbe, Celeste; Ferraresi, Virginia; Smylie, Michael; Weber, Jeffrey S.; Maio, Michele; Hosein, Fareeda; de Pril, Veerle; Kicinski, Michal; Suciu, Stefan; Testori, Alessandro.

In: European Journal of Cancer, Vol. 119, 01.09.2019, p. 1-10.

Research output: Contribution to journalArticle

Eggermont, AMM, Chiarion-Sileni, V, Grob, JJ, Dummer, R, Wolchok, JD, Schmidt, H, Hamid, O, Robert, C, Ascierto, PA, Richards, JM, Lebbe, C, Ferraresi, V, Smylie, M, Weber, JS, Maio, M, Hosein, F, de Pril, V, Kicinski, M, Suciu, S & Testori, A 2019, 'Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial', European Journal of Cancer, vol. 119, pp. 1-10. https://doi.org/10.1016/j.ejca.2019.07.001
Eggermont, Alexander M.M. ; Chiarion-Sileni, Vanna ; Grob, Jean Jacques ; Dummer, Reinhard ; Wolchok, Jedd D. ; Schmidt, Henrik ; Hamid, Omid ; Robert, Caroline ; Ascierto, Paolo Antonio ; Richards, Jon M. ; Lebbe, Celeste ; Ferraresi, Virginia ; Smylie, Michael ; Weber, Jeffrey S. ; Maio, Michele ; Hosein, Fareeda ; de Pril, Veerle ; Kicinski, Michal ; Suciu, Stefan ; Testori, Alessandro. / Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma : long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial. In: European Journal of Cancer. 2019 ; Vol. 119. pp. 1-10.
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abstract = "Background: Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3{\%} (ipilimumab) versus 4.6{\%} (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and results: A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR]: 0.75, 95{\%} confidence interval [CI]: 0.63–0.88; P < 0.001), DMFS (HR: 95{\%} CI: 0.76, 0.64–0.90; P = 0.002) and OS (HR: 0.73, 95{\%} CI: 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7{\%} absolute difference at 7 years for OS. The benefit was consistent across subgroups. Conclusions: Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.",
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T1 - Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma

T2 - long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial

AU - Eggermont, Alexander M.M.

AU - Chiarion-Sileni, Vanna

AU - Grob, Jean Jacques

AU - Dummer, Reinhard

AU - Wolchok, Jedd D.

AU - Schmidt, Henrik

AU - Hamid, Omid

AU - Robert, Caroline

AU - Ascierto, Paolo Antonio

AU - Richards, Jon M.

AU - Lebbe, Celeste

AU - Ferraresi, Virginia

AU - Smylie, Michael

AU - Weber, Jeffrey S.

AU - Maio, Michele

AU - Hosein, Fareeda

AU - de Pril, Veerle

AU - Kicinski, Michal

AU - Suciu, Stefan

AU - Testori, Alessandro

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and results: A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63–0.88; P < 0.001), DMFS (HR: 95% CI: 0.76, 0.64–0.90; P = 0.002) and OS (HR: 0.73, 95% CI: 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups. Conclusions: Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

AB - Background: Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and results: A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.63–0.88; P < 0.001), DMFS (HR: 95% CI: 0.76, 0.64–0.90; P = 0.002) and OS (HR: 0.73, 95% CI: 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups. Conclusions: Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

KW - Adjuvant therapy

KW - Ipilimumab

KW - Long-term results

KW - Melanoma

KW - Phase III trial

KW - Stage III

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