Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy

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 Richards, Celeste Lebbe, Virginia Ferraresi, M. Smylie, J. S. Weber, Michele Maio, Lars Bastholt, Laurent Mortier, Luc Thomas, S. Tahir, Axel Hauschild & 7 others Jessica C. Hassel, F. S. Hodi, C. Taitt, V. de Pril, Gaetan De Schaetzen, S. Suciu, Alessandro Testori

Research output: Contribution to journalArticle

Abstract

BACKGROUND On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P = 0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P = 0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immunerelated adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo.

Original languageEnglish
Pages (from-to)1845-1855
Number of pages11
JournalNew England Journal of Medicine
Volume375
Issue number19
DOIs
Publication statusPublished - Nov 10 2016

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Melanoma
Survival
Placebos
Recurrence
Therapeutics
Neoplasm Metastasis
Confidence Intervals
ipilimumab
Poisons
Survival Rate
Body Weight
Safety
Skin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Eggermont, A. M. M., Chiarion Sileni, V., Grob, J. J., Dummer, R., Wolchok, J. D., Schmidt, H., ... Testori, A. (2016). Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. New England Journal of Medicine, 375(19), 1845-1855. https://doi.org/10.1056/NEJMoa1611299

Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. / 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; Lebbe, Celeste; Ferraresi, Virginia; Smylie, M.; Weber, J. S.; Maio, Michele; Bastholt, Lars; Mortier, Laurent; Thomas, Luc; Tahir, S.; Hauschild, Axel; Hassel, Jessica C.; Hodi, F. S.; Taitt, C.; de Pril, V.; De Schaetzen, Gaetan; Suciu, S.; Testori, Alessandro.

In: New England Journal of Medicine, Vol. 375, No. 19, 10.11.2016, p. 1845-1855.

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, J, Lebbe, C, Ferraresi, V, Smylie, M, Weber, JS, Maio, M, Bastholt, L, Mortier, L, Thomas, L, Tahir, S, Hauschild, A, Hassel, JC, Hodi, FS, Taitt, C, de Pril, V, De Schaetzen, G, Suciu, S & Testori, A 2016, 'Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy', New England Journal of Medicine, vol. 375, no. 19, pp. 1845-1855. https://doi.org/10.1056/NEJMoa1611299
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 ; Lebbe, Celeste ; Ferraresi, Virginia ; Smylie, M. ; Weber, J. S. ; Maio, Michele ; Bastholt, Lars ; Mortier, Laurent ; Thomas, Luc ; Tahir, S. ; Hauschild, Axel ; Hassel, Jessica C. ; Hodi, F. S. ; Taitt, C. ; de Pril, V. ; De Schaetzen, Gaetan ; Suciu, S. ; Testori, Alessandro. / Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. In: New England Journal of Medicine. 2016 ; Vol. 375, No. 19. pp. 1845-1855.
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abstract = "BACKGROUND On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8{\%} in the ipilimumab group, as compared with 30.3{\%} in the placebo group (hazard ratio for recurrence or death, 0.76; 95{\%} confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4{\%} in the ipilimumab group, as compared with 54.4{\%} in the placebo group (hazard ratio for death, 0.72; 95.1{\%} CI, 0.58 to 0.88; P = 0.001). The rate of distant metastasis-free survival at 5 years was 48.3{\%} in the ipilimumab group, as compared with 38.9{\%} in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8{\%} CI, 0.64 to 0.92; P = 0.002). Adverse events of grade 3 or 4 occurred in 54.1{\%} of the patients in the ipilimumab group and in 26.2{\%} of those in the placebo group. Immunerelated adverse events of grade 3 or 4 occurred in 41.6{\%} of the patients in the ipilimumab group and in 2.7{\%} of those in the placebo group. In the ipilimumab group, 5 patients (1.1{\%}) died owing to immune-related adverse events. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo.",
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TY - JOUR

T1 - Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy

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

AU - Lebbe, Celeste

AU - Ferraresi, Virginia

AU - Smylie, M.

AU - Weber, J. S.

AU - Maio, Michele

AU - Bastholt, Lars

AU - Mortier, Laurent

AU - Thomas, Luc

AU - Tahir, S.

AU - Hauschild, Axel

AU - Hassel, Jessica C.

AU - Hodi, F. S.

AU - Taitt, C.

AU - de Pril, V.

AU - De Schaetzen, Gaetan

AU - Suciu, S.

AU - Testori, Alessandro

PY - 2016/11/10

Y1 - 2016/11/10

N2 - BACKGROUND On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P = 0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P = 0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immunerelated adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo.

AB - BACKGROUND On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma. METHODS After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety. RESULTS At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P = 0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P = 0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immunerelated adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events. CONCLUSIONS As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo.

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