Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment

a single-arm, open-label, phase II study (CheckMate 172)

Paul Nathan, Paolo A. Ascierto, John Haanen, Enrique Espinosa, Lev Demidov, Claus Garbe, Michele Guida, Paul Lorigan, Vanna Chiarion-Sileni, Helen Gogas, Michele Maio, Maria Teresa Fierro, Christoph Hoeller, Patrick Terheyden, Ralf Gutzmer, Tormod K. Guren, Dimitrios Bafaloukos, Piotr Rutkowski, Ruth Plummer, Ashita Waterston & 8 others Martin Kaatz, Mario Mandala, Ivan Marquez-Rodas, Eva Muñoz-Couselo, Reinhard Dummer, Elena Grigoryeva, Tina C. Young, Dirk Schadendorf

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7%]), ocular melanoma (n = 103 [10.2%]), mucosal melanoma (n = 63 [6.3%]), acral cutaneous melanoma (n = 55 [5.5%]) and other melanoma subtypes (n = 64 [6.3%]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5% and 59.0%, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8% and 31.5%, respectively. Conclusions: The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID: : NCT02156804.

Original languageEnglish
Pages (from-to)168-178
Number of pages11
JournalEuropean Journal of Cancer
Volume119
DOIs
Publication statusPublished - Sep 1 2019

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Melanoma
Safety
Therapeutics
Skin
ipilimumab
nivolumab
Survival
Extremities
Survival Rate
Incidence
Multicenter Studies

Keywords

  • Acral
  • Advanced melanoma
  • Ipilimumab
  • Mucosal
  • Nivolumab
  • Ocular

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment : a single-arm, open-label, phase II study (CheckMate 172). / Nathan, Paul; Ascierto, Paolo A.; Haanen, John; Espinosa, Enrique; Demidov, Lev; Garbe, Claus; Guida, Michele; Lorigan, Paul; Chiarion-Sileni, Vanna; Gogas, Helen; Maio, Michele; Fierro, Maria Teresa; Hoeller, Christoph; Terheyden, Patrick; Gutzmer, Ralf; Guren, Tormod K.; Bafaloukos, Dimitrios; Rutkowski, Piotr; Plummer, Ruth; Waterston, Ashita; Kaatz, Martin; Mandala, Mario; Marquez-Rodas, Ivan; Muñoz-Couselo, Eva; Dummer, Reinhard; Grigoryeva, Elena; Young, Tina C.; Schadendorf, Dirk.

In: European Journal of Cancer, Vol. 119, 01.09.2019, p. 168-178.

Research output: Contribution to journalArticle

Nathan, P, Ascierto, PA, Haanen, J, Espinosa, E, Demidov, L, Garbe, C, Guida, M, Lorigan, P, Chiarion-Sileni, V, Gogas, H, Maio, M, Fierro, MT, Hoeller, C, Terheyden, P, Gutzmer, R, Guren, TK, Bafaloukos, D, Rutkowski, P, Plummer, R, Waterston, A, Kaatz, M, Mandala, M, Marquez-Rodas, I, Muñoz-Couselo, E, Dummer, R, Grigoryeva, E, Young, TC & Schadendorf, D 2019, 'Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment: a single-arm, open-label, phase II study (CheckMate 172)', European Journal of Cancer, vol. 119, pp. 168-178. https://doi.org/10.1016/j.ejca.2019.07.010
Nathan, Paul ; Ascierto, Paolo A. ; Haanen, John ; Espinosa, Enrique ; Demidov, Lev ; Garbe, Claus ; Guida, Michele ; Lorigan, Paul ; Chiarion-Sileni, Vanna ; Gogas, Helen ; Maio, Michele ; Fierro, Maria Teresa ; Hoeller, Christoph ; Terheyden, Patrick ; Gutzmer, Ralf ; Guren, Tormod K. ; Bafaloukos, Dimitrios ; Rutkowski, Piotr ; Plummer, Ruth ; Waterston, Ashita ; Kaatz, Martin ; Mandala, Mario ; Marquez-Rodas, Ivan ; Muñoz-Couselo, Eva ; Dummer, Reinhard ; Grigoryeva, Elena ; Young, Tina C. ; Schadendorf, Dirk. / Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment : a single-arm, open-label, phase II study (CheckMate 172). In: European Journal of Cancer. 2019 ; Vol. 119. pp. 168-178.
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abstract = "Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7{\%}]), ocular melanoma (n = 103 [10.2{\%}]), mucosal melanoma (n = 63 [6.3{\%}]), acral cutaneous melanoma (n = 55 [5.5{\%}]) and other melanoma subtypes (n = 64 [6.3{\%}]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5{\%} and 59.0{\%}, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8{\%} and 31.5{\%}, respectively. Conclusions: The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID: : NCT02156804.",
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T1 - Safety and efficacy of nivolumab in patients with rare melanoma subtypes who progressed on or after ipilimumab treatment

T2 - a single-arm, open-label, phase II study (CheckMate 172)

AU - Nathan, Paul

AU - Ascierto, Paolo A.

AU - Haanen, John

AU - Espinosa, Enrique

AU - Demidov, Lev

AU - Garbe, Claus

AU - Guida, Michele

AU - Lorigan, Paul

AU - Chiarion-Sileni, Vanna

AU - Gogas, Helen

AU - Maio, Michele

AU - Fierro, Maria Teresa

AU - Hoeller, Christoph

AU - Terheyden, Patrick

AU - Gutzmer, Ralf

AU - Guren, Tormod K.

AU - Bafaloukos, Dimitrios

AU - Rutkowski, Piotr

AU - Plummer, Ruth

AU - Waterston, Ashita

AU - Kaatz, Martin

AU - Mandala, Mario

AU - Marquez-Rodas, Ivan

AU - Muñoz-Couselo, Eva

AU - Dummer, Reinhard

AU - Grigoryeva, Elena

AU - Young, Tina C.

AU - Schadendorf, Dirk

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7%]), ocular melanoma (n = 103 [10.2%]), mucosal melanoma (n = 63 [6.3%]), acral cutaneous melanoma (n = 55 [5.5%]) and other melanoma subtypes (n = 64 [6.3%]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5% and 59.0%, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8% and 31.5%, respectively. Conclusions: The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID: : NCT02156804.

AB - Background: Nivolumab has been widely studied in non-acral cutaneous melanoma; however, limited data are available in other melanoma subtypes. We report outcomes by melanoma subtype in patients who received nivolumab after progression on prior ipilimumab. Patients and methods: CheckMate 172 was a phase II, single-arm, open-label, multicentre study that evaluated nivolumab in patients with advanced melanoma who progressed on or after ipilimumab. Patients received 3 mg/kg of nivolumab, every 2 weeks for up to 2 years. The primary end-point was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: Among 1008 treated patients, we report data on patients with non-acral cutaneous melanoma (n = 723 [71.7%]), ocular melanoma (n = 103 [10.2%]), mucosal melanoma (n = 63 [6.3%]), acral cutaneous melanoma (n = 55 [5.5%]) and other melanoma subtypes (n = 64 [6.3%]). There were no meaningful differences in the incidence of grade ≥3, treatment-related select AEs among melanoma subtypes or compared with the total population. No new safety signals emerged. At a minimum follow-up of 18 months, median overall survival was 25.3 months for non-acral cutaneous melanoma and 25.8 months for acral cutaneous melanoma, with 18-month overall survival rates of 57.5% and 59.0%, respectively. Median overall survival was 12.6 months for ocular melanoma and 11.5 months for mucosal melanoma, with 18-month overall survival rates of 34.8% and 31.5%, respectively. Conclusions: The safety profile of nivolumab after ipilimumab is similar across melanoma subtypes. Compared with non-acral cutaneous melanoma, patients with acral cutaneous melanoma had similar survival outcomes, whereas those with ocular and mucosal melanoma had lower median overall survival. ClinicalTrials.gov ID: : NCT02156804.

KW - Acral

KW - Advanced melanoma

KW - Ipilimumab

KW - Mucosal

KW - Nivolumab

KW - Ocular

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