Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

Anouk Jochems; Esther Bastiaannet; Maureen J.B. Aarts; Alexander C.J. van Akkooi; Franchette W.P.J. van den Berkmortel; Marye J. Boers-Sonderen; Alfonsus J.M. van den Eertwegh; Nienke G. de Glas; Jan Willem B. de Groot; John B.A.G. Haanen; Geke A.P. Hospers; Jacobus J.M. van der Hoeven; Djura Piersma; Rozemarijn S. van Rijn; Karijn P.M. Suijkerbuijk; Albert J. ten Tije; Astrid A.M. van der Veldt; Gerard Vreugdenhil; Michiel C.T. van Zeijl; Ellen Kapiteijn; Michel W.J.M. Wouters

doi:10.1016/j.jgo.2021.04.006

Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

Anouk Jochems^*, Esther Bastiaannet, Maureen J.B. Aarts, Alexander C.J. van Akkooi, Franchette W.P.J. van den Berkmortel, Marye J. Boers-Sonderen, Alfonsus J.M. van den Eertwegh, Nienke G. de Glas, Jan Willem B. de Groot, John B.A.G. Haanen, Geke A.P. Hospers, Jacobus J.M. van der Hoeven, Djura Piersma, Rozemarijn S. van Rijn, Karijn P.M. Suijkerbuijk, Albert J. ten Tije, Astrid A.M. van der Veldt, Gerard Vreugdenhil, Michiel C.T. van Zeijl, Ellen KapiteijnMichel W.J.M. Wouters

^*Corresponding author for this work

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Abstract

Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66–74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1–19.3) in patients ≥75 years versus 26.7% (23.1–30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50–1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0–39.2) versus 34.0% (29.7–38.2), HR 1.26 (95% CI 1.07–1.49), p = 0.005 with an adjusted HR of 1.21 (1.00–1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.

Original language	English
Pages (from-to)	1031-1038
Number of pages	8
Journal	Journal of Geriatric Oncology
Volume	12
Issue number	7
DOIs	https://doi.org/10.1016/j.jgo.2021.04.006
Publication status	Published - 1 Sept 2021

Bibliographical note

Funding Information:
The Netherlands Organisation for Health Research and Development funded the start-up of the DMTR (grant number 836002002 ). This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation the DMTR was sponsored by BMS , GSK (later acquired by Novartis), Roche Nederland BV and MSD (from 2015). Roche Nederland B.V. stopped and Pierre Fabre started funding of the DMTR in 2019. This manuscript received no external funding.

Funding Information:
Conceptualization : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Data curation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH), Maureen J.B Aarts (MA), Franchette W.P.J. van den Berkmortel (FB), Marye J. Boers-Sonderen (MB), Alfonsus J.M. van den Eertwegh (AE), Nienke A. de Glas (NG), Jan Willem B. de Groot (JG), John B.A.G. Haanen (JH), Geke A.P. Hospers (GH), Djura Piersma (DP), Rozemarijn S. van Rijn (RR), Karijn P.M. Suijkerbuijk (KS), Albert Jan ten Tije (AT), Astrid A.M. van der Veldt (AV), Gerard Vreugdenhil (GV), Michiel C.T. van der Zeijl (MZ). Formal analysis : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Funding acquisition : None for this article in particular. The DMTR was funded with a grant from the Netherlands Organization for Health Research and Development. Investigation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Methodology : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Project administration : Anouk Jochems (AJ). Resources : The Dutch Melanoma Treatment Registry. Software : STATA/SE (version 12.0, Statacorp LP, Texas, USA). Supervision : Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Validation : the manuscript has been reviewed and approved by all co- authors. Visualization : Anouk Jochems (AJ), Esther Bastiaannet (EB). Writing Original Draft : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Writing review & editing : the manuscript has been reviewed and approved by all co-authors. The first author (AJ) edited all feedback and changes.

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Outcomes for systemic therapy in older patients with metastatic melanomaFinal published version, 1.11 MBLicence: CC BY

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Jochems, A., Bastiaannet, E., Aarts, M. J. B., van Akkooi, A. C. J., van den Berkmortel, F. W. P. J., Boers-Sonderen, M. J., van den Eertwegh, A. J. M., de Glas, N. G., de Groot, J. W. B., Haanen, J. B. A. G., Hospers, G. A. P., van der Hoeven, J. J. M., Piersma, D., van Rijn, R. S., Suijkerbuijk, K. P. M., ten Tije, A. J., van der Veldt, A. A. M., Vreugdenhil, G., van Zeijl, M. C. T., ... Wouters, M. W. J. M. (2021). Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry. Journal of Geriatric Oncology, 12(7), 1031-1038. https://doi.org/10.1016/j.jgo.2021.04.006

@article{492640ef87334f75bd9b0a077216a374,

title = "Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry",

abstract = "Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66–74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1–19.3) in patients ≥75 years versus 26.7% (23.1–30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50–1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0–39.2) versus 34.0% (29.7–38.2), HR 1.26 (95% CI 1.07–1.49), p = 0.005 with an adjusted HR of 1.21 (1.00–1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.",

author = "Anouk Jochems and Esther Bastiaannet and Aarts, {Maureen J.B.} and {van Akkooi}, {Alexander C.J.} and {van den Berkmortel}, {Franchette W.P.J.} and Boers-Sonderen, {Marye J.} and {van den Eertwegh}, {Alfonsus J.M.} and {de Glas}, {Nienke G.} and {de Groot}, {Jan Willem B.} and Haanen, {John B.A.G.} and Hospers, {Geke A.P.} and {van der Hoeven}, {Jacobus J.M.} and Djura Piersma and {van Rijn}, {Rozemarijn S.} and Suijkerbuijk, {Karijn P.M.} and {ten Tije}, {Albert J.} and {van der Veldt}, {Astrid A.M.} and Gerard Vreugdenhil and {van Zeijl}, {Michiel C.T.} and Ellen Kapiteijn and Wouters, {Michel W.J.M.}",

note = "Funding Information: The Netherlands Organisation for Health Research and Development funded the start-up of the DMTR (grant number 836002002 ). This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation the DMTR was sponsored by BMS , GSK (later acquired by Novartis), Roche Nederland BV and MSD (from 2015). Roche Nederland B.V. stopped and Pierre Fabre started funding of the DMTR in 2019. This manuscript received no external funding. Funding Information: Conceptualization : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Data curation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH), Maureen J.B Aarts (MA), Franchette W.P.J. van den Berkmortel (FB), Marye J. Boers-Sonderen (MB), Alfonsus J.M. van den Eertwegh (AE), Nienke A. de Glas (NG), Jan Willem B. de Groot (JG), John B.A.G. Haanen (JH), Geke A.P. Hospers (GH), Djura Piersma (DP), Rozemarijn S. van Rijn (RR), Karijn P.M. Suijkerbuijk (KS), Albert Jan ten Tije (AT), Astrid A.M. van der Veldt (AV), Gerard Vreugdenhil (GV), Michiel C.T. van der Zeijl (MZ). Formal analysis : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Funding acquisition : None for this article in particular. The DMTR was funded with a grant from the Netherlands Organization for Health Research and Development. Investigation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Methodology : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Project administration : Anouk Jochems (AJ). Resources : The Dutch Melanoma Treatment Registry. Software : STATA/SE (version 12.0, Statacorp LP, Texas, USA). Supervision : Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Validation : the manuscript has been reviewed and approved by all co- authors. Visualization : Anouk Jochems (AJ), Esther Bastiaannet (EB). Writing Original Draft : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Writing review & editing : the manuscript has been reviewed and approved by all co-authors. The first author (AJ) edited all feedback and changes. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = sep,

day = "1",

doi = "10.1016/j.jgo.2021.04.006",

language = "English",

volume = "12",

pages = "1031--1038",

journal = "Journal of Geriatric Oncology",

issn = "1879-4068",

publisher = "Elsevier Ltd.",

number = "7",

}

Jochems, A, Bastiaannet, E, Aarts, MJB, van Akkooi, ACJ, van den Berkmortel, FWPJ, Boers-Sonderen, MJ, van den Eertwegh, AJM, de Glas, NG, de Groot, JWB, Haanen, JBAG, Hospers, GAP, van der Hoeven, JJM, Piersma, D, van Rijn, RS, Suijkerbuijk, KPM, ten Tije, AJ, van der Veldt, AAM, Vreugdenhil, G, van Zeijl, MCT, Kapiteijn, E & Wouters, MWJM 2021, 'Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry', Journal of Geriatric Oncology, vol. 12, no. 7, pp. 1031-1038. https://doi.org/10.1016/j.jgo.2021.04.006

TY - JOUR

T1 - Outcomes for systemic therapy in older patients with metastatic melanoma

T2 - Results from the Dutch Melanoma Treatment Registry

AU - Jochems, Anouk

AU - Bastiaannet, Esther

AU - Aarts, Maureen J.B.

AU - van Akkooi, Alexander C.J.

AU - van den Berkmortel, Franchette W.P.J.

AU - Boers-Sonderen, Marye J.

AU - van den Eertwegh, Alfonsus J.M.

AU - de Glas, Nienke G.

AU - de Groot, Jan Willem B.

AU - Haanen, John B.A.G.

AU - Hospers, Geke A.P.

AU - van der Hoeven, Jacobus J.M.

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S.

AU - Suijkerbuijk, Karijn P.M.

AU - ten Tije, Albert J.

AU - van der Veldt, Astrid A.M.

AU - Vreugdenhil, Gerard

AU - van Zeijl, Michiel C.T.

AU - Kapiteijn, Ellen

AU - Wouters, Michel W.J.M.

N1 - Funding Information: The Netherlands Organisation for Health Research and Development funded the start-up of the DMTR (grant number 836002002 ). This grant was awarded under the effectiveness research for high-cost medicine programme. From its foundation the DMTR was sponsored by BMS , GSK (later acquired by Novartis), Roche Nederland BV and MSD (from 2015). Roche Nederland B.V. stopped and Pierre Fabre started funding of the DMTR in 2019. This manuscript received no external funding. Funding Information: Conceptualization : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Data curation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH), Maureen J.B Aarts (MA), Franchette W.P.J. van den Berkmortel (FB), Marye J. Boers-Sonderen (MB), Alfonsus J.M. van den Eertwegh (AE), Nienke A. de Glas (NG), Jan Willem B. de Groot (JG), John B.A.G. Haanen (JH), Geke A.P. Hospers (GH), Djura Piersma (DP), Rozemarijn S. van Rijn (RR), Karijn P.M. Suijkerbuijk (KS), Albert Jan ten Tije (AT), Astrid A.M. van der Veldt (AV), Gerard Vreugdenhil (GV), Michiel C.T. van der Zeijl (MZ). Formal analysis : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Funding acquisition : None for this article in particular. The DMTR was funded with a grant from the Netherlands Organization for Health Research and Development. Investigation : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Methodology : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Project administration : Anouk Jochems (AJ). Resources : The Dutch Melanoma Treatment Registry. Software : STATA/SE (version 12.0, Statacorp LP, Texas, USA). Supervision : Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Validation : the manuscript has been reviewed and approved by all co- authors. Visualization : Anouk Jochems (AJ), Esther Bastiaannet (EB). Writing Original Draft : Anouk Jochems (AJ), Esther Bastiaannet (EB), Ellen Kapiteijn (EK), Michel W.J.M Wouters (MW), Jacobus J.M. van der Hoeven (JvdH). Writing review & editing : the manuscript has been reviewed and approved by all co-authors. The first author (AJ) edited all feedback and changes. Publisher Copyright: © 2021 The Authors

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66–74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1–19.3) in patients ≥75 years versus 26.7% (23.1–30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50–1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0–39.2) versus 34.0% (29.7–38.2), HR 1.26 (95% CI 1.07–1.49), p = 0.005 with an adjusted HR of 1.21 (1.00–1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.

AB - Background: The incidence of metastatic melanoma is increasing in all ages. Multiple trials with targeted drugs and immune checkpoint inhibitors showed improved survival in metastatic melanoma. However, patients aged ≥75 years are often under-represented in clinical trials, therefore raising questions on safety and efficacy of treatment. Patients and methods: We analyzed a real-world cohort of 3054 patients with metastatic melanoma stratified for age (≤65 years, 66–74 years and ≥ 75 years), and BRAF status, providing data on treatment strategies, toxicity, and survival. Kaplan Meier curves and Cox Proportional Hazard Models were used to present overall survival (OS) and Melanoma Specific Survival (MSS). Results: Overall, 52.2% of patients were ≤ 65 years and 18.4% of patients ≥75 years. BRAF mutated tumors were found less often in patients ≥75 years: 34.5% versus 65% in patients ≤65 years. Patients ≥75 years received systemic therapy less frequently compared to their younger counterparts independent of the BRAF status. When receiving treatment, no statistical significant difference in grade 3 or 4 toxicity was observed. Three year Overall Survival rate was 13.7% (9.1–19.3) in patients ≥75 years versus 26.7% (23.1–30.4) in patients ≤65 years, with a Hazard Ratio (HR) of 1.71 (95%CI 1.50–1.95), p < 0.001. Three year Melanoma Specific Survival was 30.4% (22.0–39.2) versus 34.0% (29.7–38.2), HR 1.26 (95% CI 1.07–1.49), p = 0.005 with an adjusted HR of 1.21 (1.00–1.47), p = 0.049. Conclusion: Patients with metastatic melanoma ≥75 years are less frequently treated, but when treated there is no statistical significant increase in toxicity and only a borderline statistical significant difference in Melanoma Specific Survival was seen, compared to younger patients.

UR - http://www.scopus.com/inward/record.url?scp=85106352173&partnerID=8YFLogxK

U2 - 10.1016/j.jgo.2021.04.006

DO - 10.1016/j.jgo.2021.04.006

M3 - Article

C2 - 34020909

AN - SCOPUS:85106352173

SN - 1879-4068

VL - 12

SP - 1031

EP - 1038

JO - Journal of Geriatric Oncology

JF - Journal of Geriatric Oncology

IS - 7

ER -

Outcomes for systemic therapy in older patients with metastatic melanoma: Results from the Dutch Melanoma Treatment Registry

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