Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma

Robert Mason, Helen C. Dearden, Bella Nguyen, Jennifer S. Oon, Jessica Louise Smith, Manreet Randhawa, Andrew Mant, Lydai Warburton, Serigne Lo, Tarek Meniawy, Alexander Guminski, Phillip Parente, Sayed Ali, Andrew Haydon, Georgina V. Long, Matteo S. Carlino, Michael Millward, Victoria G. Atkinson, Alexander M. Menzies

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Abstract

The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.

Original languageEnglish
JournalPigment Cell and Melanoma Research
DOIs
Publication statusE-pub ahead of print - 6 Oct 2019

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Mitogen-Activated Protein Kinase Kinases
Melanoma
Proto-Oncogene Proteins c-akt
Protein-Serine-Threonine Kinases
Therapeutics
Toxicity
Population
Disease-Free Survival
nivolumab
ipilimumab
Demography
Safety
Survival

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Mason, R., Dearden, H. C., Nguyen, B., Oon, J. S., Smith, J. L., Randhawa, M., ... Menzies, A. M. (2019). Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma. Pigment Cell and Melanoma Research. https://doi.org/10.1111/pcmr.12831
Mason, Robert ; Dearden, Helen C. ; Nguyen, Bella ; Oon, Jennifer S. ; Smith, Jessica Louise ; Randhawa, Manreet ; Mant, Andrew ; Warburton, Lydai ; Lo, Serigne ; Meniawy, Tarek ; Guminski, Alexander ; Parente, Phillip ; Ali, Sayed ; Haydon, Andrew ; Long, Georgina V. ; Carlino, Matteo S. ; Millward, Michael ; Atkinson, Victoria G. ; Menzies, Alexander M. / Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma. In: Pigment Cell and Melanoma Research. 2019.
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abstract = "The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39{\%} were treatment-na{\"i}ve and 22{\%} failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67{\%} of patients, grade 3–5 in 38{\%}. The overall objective response rate was 41{\%}, 57{\%} in treatment-na{\"i}ve and 21{\%} in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95{\%} CI, 3.0–6.0) in the whole cohort, 11.0 months (95{\%} CI, 6.0-NR) in treatment-na{\"i}ve and 2.0 months (95{\%} CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.",
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author = "Robert Mason and Dearden, {Helen C.} and Bella Nguyen and Oon, {Jennifer S.} and Smith, {Jessica Louise} and Manreet Randhawa and Andrew Mant and Lydai Warburton and Serigne Lo and Tarek Meniawy and Alexander Guminski and Phillip Parente and Sayed Ali and Andrew Haydon and Long, {Georgina V.} and Carlino, {Matteo S.} and Michael Millward and Atkinson, {Victoria G.} and Menzies, {Alexander M.}",
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Mason, R, Dearden, HC, Nguyen, B, Oon, JS, Smith, JL, Randhawa, M, Mant, A, Warburton, L, Lo, S, Meniawy, T, Guminski, A, Parente, P, Ali, S, Haydon, A, Long, GV, Carlino, MS, Millward, M, Atkinson, VG & Menzies, AM 2019, 'Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma' Pigment Cell and Melanoma Research. https://doi.org/10.1111/pcmr.12831

Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma. / Mason, Robert; Dearden, Helen C.; Nguyen, Bella; Oon, Jennifer S.; Smith, Jessica Louise; Randhawa, Manreet; Mant, Andrew; Warburton, Lydai; Lo, Serigne; Meniawy, Tarek; Guminski, Alexander; Parente, Phillip; Ali, Sayed; Haydon, Andrew; Long, Georgina V.; Carlino, Matteo S.; Millward, Michael; Atkinson, Victoria G.; Menzies, Alexander M.

In: Pigment Cell and Melanoma Research, 06.10.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Combined ipilimumab and nivolumab first-line and after BRAF-targeted therapy in advanced melanoma

AU - Mason, Robert

AU - Dearden, Helen C.

AU - Nguyen, Bella

AU - Oon, Jennifer S.

AU - Smith, Jessica Louise

AU - Randhawa, Manreet

AU - Mant, Andrew

AU - Warburton, Lydai

AU - Lo, Serigne

AU - Meniawy, Tarek

AU - Guminski, Alexander

AU - Parente, Phillip

AU - Ali, Sayed

AU - Haydon, Andrew

AU - Long, Georgina V.

AU - Carlino, Matteo S.

AU - Millward, Michael

AU - Atkinson, Victoria G.

AU - Menzies, Alexander M.

PY - 2019/10/6

Y1 - 2019/10/6

N2 - The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.

AB - The combination of ipilimumab and nivolumab is a highly active systemic therapy for metastatic melanoma but can cause significant toxicity. We explore the safety and efficacy of this treatment in routine clinical practice, particularly in the setting of serine/threonine-protein kinase B-Raf (BRAF)-targeted therapy. Consecutive patients with unresectable stage IIIC/IV melanoma commenced on ipilimumab and nivolumab across 10 tertiary melanoma institutions in Australia were identified retrospectively. Data collected included demographics, response and survival outcomes. A total of 152 patients were included for analysis, 39% were treatment-naïve and 22% failed first-line BRAF/MEK inhibitors. Treatment-related adverse events occurred in 67% of patients, grade 3–5 in 38%. The overall objective response rate was 41%, 57% in treatment-naïve and 21% in BRAF/MEK failure patients. Median progression-free survival was 4.0 months (95% CI, 3.0–6.0) in the whole cohort, 11.0 months (95% CI, 6.0-NR) in treatment-naïve and 2.0 months (95% CI, 1.4–4.6) in BRAF/MEK failure patients. The combination of ipilimumab and nivolumab can be used safely and effectively in a real-world population. While first-line efficacy appears comparable to trial populations, BRAF-mutant patients failing prior BRAF/MEK inhibitors show less response.

KW - BRAF

KW - immunotherapy

KW - ipilimumab

KW - melanoma

KW - nivolumab

KW - targeted therapy

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U2 - 10.1111/pcmr.12831

DO - 10.1111/pcmr.12831

M3 - Article

JO - PIGMENT CELL & MELANOMA RESEARCH

JF - PIGMENT CELL & MELANOMA RESEARCH

SN - 0893-5785

ER -