Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

Jesper van Breeschoten; Michel W J M Wouters; Liesbeth C de Wreede; Doranne H Hilarius; John B Haanen; Christian U Blank; Maureen J B Aarts; Franchette W P J van den Berkmortel; Jan-Willem B de Groot; Geke A P Hospers; Ellen Kapiteijn; Djura Piersma; Rozemarijn S van Rijn; Karijn P M Suijkerbuijk; Willeke A M Blokx; Albert J Ten Tije; Astrid A M van der Veldt; Gerard Vreugdenhil; Marye J Boers; Alfons J M van den Eertwegh

doi:10.1097/COC.0000000000000786

Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

Jesper van Breeschoten, Michel W J M Wouters, Liesbeth C de Wreede, Doranne H Hilarius, John B Haanen, Christian U Blank, Maureen J B Aarts, Franchette W P J van den Berkmortel, Jan-Willem B de Groot, Geke A P Hospers, Ellen Kapiteijn, Djura Piersma, Rozemarijn S van Rijn, Karijn P M Suijkerbuijk, Willeke A M Blokx, Albert J Ten Tije, Astrid A M van der Veldt, Gerard Vreugdenhil, Marye J Boers, Alfons J M van den Eertwegh

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

OBJECTIVE: The aim of this study was to evaluate treatment patterns and overall survival (OS) of patients with BRAFV600 wild-type and BRAFV600-mutant advanced melanoma in the Netherlands.

METHODS: We selected patients of 18 years and over, diagnosed between 2016 and 2017 with unresectable stage IIIC or IV melanoma, registered in the Dutch Melanoma Treatment Registry. To assess the association of BRAFV600-mutation status with OS we used the Cox proportional-hazards model.

RESULTS: A total of 642 BRAFV600 wild-type and 853 mutant patients were included in the analysis. Median OS did not differ significantly between both groups, 15.2 months (95% confidence interval [CI]: 13.2-19.2) versus 20.6 months (95% CI: 18.3-25.0). Survival rates at 6 and 12 months were significantly lower for BRAFV600 wild-type patients compared with BRAFV600-mutant patients, 72.0% (95% CI: 68.6-75.6) and 56.0% (95% CI: 52.2-60.0) versus 83.4% (95% CI: 80.9-85.9) and 65.7% (95% CI: 62.6-69.0). Two-year survival was not significantly different between both groups, 41.1% (95% CI: 37.2-45.3) versus 47.0% (95% CI: 43.6-60.6). Between 0 and 10 months, BRAFV600 wild-type patients had a decreased survival with a hazard ratio for OS of 2.00 (95% CI: 1.62-2.46) but this effect disappeared after 10 months. At 12 months, BRAFV600-mutant patients had started with second-line systemic treatment more often compared with BRAFV600 wild-type patients (50% vs. 19%).

CONCLUSION: These results suggest that advanced BRAFV600 wild-type melanoma patients have worse survival than BRAFV600-mutated patients during the first 10 months after diagnosis because of less available treatment options.

Original language	English
Pages (from-to)	82-89
Number of pages	8
Journal	American Journal of Clinical Oncology
Volume	44
Issue number	2
Early online date	15 Dec 2020
DOIs	https://doi.org/10.1097/COC.0000000000000786
Publication status	Published - 1 Feb 2021

Keywords

BRAF mutation
BRAF/MEK inhibitors
CTLA-4 inhibitor
National Registry
advanced melanoma
anti-PD-1-ligands
checkpoint inhibitors

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10.1097/COC.0000000000000786

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van Breeschoten, J., Wouters, M. W. J. M., de Wreede, L. C., Hilarius, D. H., Haanen, J. B., Blank, C. U., Aarts, M. J. B., van den Berkmortel, F. W. P. J., de Groot, J.-W. B., Hospers, G. A. P., Kapiteijn, E., Piersma, D., van Rijn, R. S., Suijkerbuijk, K. P. M., Blokx, W. A. M., Ten Tije, A. J., van der Veldt, A. A. M., Vreugdenhil, G., Boers, M. J., & van den Eertwegh, A. J. M. (2021). Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status. American Journal of Clinical Oncology, 44(2), 82-89. https://doi.org/10.1097/COC.0000000000000786

@article{b7b24d5e3e934e68a229ec795ab8a535,

title = "Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status",

abstract = "OBJECTIVE: The aim of this study was to evaluate treatment patterns and overall survival (OS) of patients with BRAFV600 wild-type and BRAFV600-mutant advanced melanoma in the Netherlands.METHODS: We selected patients of 18 years and over, diagnosed between 2016 and 2017 with unresectable stage IIIC or IV melanoma, registered in the Dutch Melanoma Treatment Registry. To assess the association of BRAFV600-mutation status with OS we used the Cox proportional-hazards model.RESULTS: A total of 642 BRAFV600 wild-type and 853 mutant patients were included in the analysis. Median OS did not differ significantly between both groups, 15.2 months (95% confidence interval [CI]: 13.2-19.2) versus 20.6 months (95% CI: 18.3-25.0). Survival rates at 6 and 12 months were significantly lower for BRAFV600 wild-type patients compared with BRAFV600-mutant patients, 72.0% (95% CI: 68.6-75.6) and 56.0% (95% CI: 52.2-60.0) versus 83.4% (95% CI: 80.9-85.9) and 65.7% (95% CI: 62.6-69.0). Two-year survival was not significantly different between both groups, 41.1% (95% CI: 37.2-45.3) versus 47.0% (95% CI: 43.6-60.6). Between 0 and 10 months, BRAFV600 wild-type patients had a decreased survival with a hazard ratio for OS of 2.00 (95% CI: 1.62-2.46) but this effect disappeared after 10 months. At 12 months, BRAFV600-mutant patients had started with second-line systemic treatment more often compared with BRAFV600 wild-type patients (50% vs. 19%).CONCLUSION: These results suggest that advanced BRAFV600 wild-type melanoma patients have worse survival than BRAFV600-mutated patients during the first 10 months after diagnosis because of less available treatment options.",

keywords = "BRAF mutation, BRAF/MEK inhibitors, CTLA-4 inhibitor, National Registry, advanced melanoma, anti-PD-1-ligands, checkpoint inhibitors",

author = "{van Breeschoten}, Jesper and Wouters, {Michel W J M} and {de Wreede}, {Liesbeth C} and Hilarius, {Doranne H} and Haanen, {John B} and Blank, {Christian U} and Aarts, {Maureen J B} and {van den Berkmortel}, {Franchette W P J} and {de Groot}, {Jan-Willem B} and Hospers, {Geke A P} and Ellen Kapiteijn and Djura Piersma and {van Rijn}, {Rozemarijn S} and Suijkerbuijk, {Karijn P M} and Blokx, {Willeke A M} and {Ten Tije}, {Albert J} and {van der Veldt}, {Astrid A M} and Gerard Vreugdenhil and Boers, {Marye J} and {van den Eertwegh}, {Alfons J M}",

note = "Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing Foundation received a startup grant from the governmental organization The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019 and Pierre Fabre started funding of the DMTR in 2019. Funding Information: J.B.H. has advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics and has received research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, Neon Therapeutics. All grants were paid to the institutions. C.U.B. has advisory relationships with, Bristol-Myers Squibb, Genmab, GSK, Lilly, MSD, Roche, Novartis, Pfizer and grant support by BMS, Novartis, and NanoString. J.-W.B.d.G. has received personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre Fabre, Servier, MSD, Novartis. G.A.P.H. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, BMS. She received honoraria from Novartis, Pierre Fabre, and Roche and has received research grants not related to this paper from Bristol-Myers Squibb, Seerave. A.A.M.v.d.V. has consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai. E.K. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck, Pierre Fabre, EISAI, Bayer, Genzyme-Sanofi and received research grants not related to this paper from Novartis and Bristol-Myers Squibb. K.P.M.S. has consulting/advisory relationships with BMS and MSD. She received honoraria from Novartis, Pierre Fabre, and Roche. A.J.M.v.d.E. has consulting/advisory relationships with BMS, Roche, MSD, and Novartis. He received a study grant from Roche. The funders had no role in the writing of this article or decision to submit it for publication. The other authors declare no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 Lippincott Williams and Wilkins. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = feb,

day = "1",

doi = "10.1097/COC.0000000000000786",

language = "English",

volume = "44",

pages = "82--89",

journal = "American Journal of Clinical Oncology",

issn = "0277-3732",

publisher = "Lippincott Williams & Wilkins",

number = "2",

}

van Breeschoten, J, Wouters, MWJM, de Wreede, LC, Hilarius, DH, Haanen, JB, Blank, CU, Aarts, MJB, van den Berkmortel, FWPJ, de Groot, J-WB, Hospers, GAP, Kapiteijn, E, Piersma, D, van Rijn, RS, Suijkerbuijk, KPM , Blokx, WAM, Ten Tije, AJ, van der Veldt, AAM, Vreugdenhil, G, Boers, MJ & van den Eertwegh, AJM 2021, 'Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status', American Journal of Clinical Oncology, vol. 44, no. 2, pp. 82-89. https://doi.org/10.1097/COC.0000000000000786

TY - JOUR

T1 - Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

AU - van Breeschoten, Jesper

AU - Wouters, Michel W J M

AU - de Wreede, Liesbeth C

AU - Hilarius, Doranne H

AU - Haanen, John B

AU - Blank, Christian U

AU - Aarts, Maureen J B

AU - van den Berkmortel, Franchette W P J

AU - de Groot, Jan-Willem B

AU - Hospers, Geke A P

AU - Kapiteijn, Ellen

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S

AU - Suijkerbuijk, Karijn P M

AU - Blokx, Willeke A M

AU - Ten Tije, Albert J

AU - van der Veldt, Astrid A M

AU - Vreugdenhil, Gerard

AU - Boers, Marye J

AU - van den Eertwegh, Alfons J M

N1 - Funding Information: For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing Foundation received a startup grant from the governmental organization The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019 and Pierre Fabre started funding of the DMTR in 2019. Funding Information: J.B.H. has advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics and has received research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, Neon Therapeutics. All grants were paid to the institutions. C.U.B. has advisory relationships with, Bristol-Myers Squibb, Genmab, GSK, Lilly, MSD, Roche, Novartis, Pfizer and grant support by BMS, Novartis, and NanoString. J.-W.B.d.G. has received personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre Fabre, Servier, MSD, Novartis. G.A.P.H. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, Novartis, BMS. She received honoraria from Novartis, Pierre Fabre, and Roche and has received research grants not related to this paper from Bristol-Myers Squibb, Seerave. A.A.M.v.d.V. has consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre Fabre, Pfizer, Sanofi, Ipsen, Eisai. E.K. has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck, Pierre Fabre, EISAI, Bayer, Genzyme-Sanofi and received research grants not related to this paper from Novartis and Bristol-Myers Squibb. K.P.M.S. has consulting/advisory relationships with BMS and MSD. She received honoraria from Novartis, Pierre Fabre, and Roche. A.J.M.v.d.E. has consulting/advisory relationships with BMS, Roche, MSD, and Novartis. He received a study grant from Roche. The funders had no role in the writing of this article or decision to submit it for publication. The other authors declare no conflicts of interest. Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/1

Y1 - 2021/2/1

N2 - OBJECTIVE: The aim of this study was to evaluate treatment patterns and overall survival (OS) of patients with BRAFV600 wild-type and BRAFV600-mutant advanced melanoma in the Netherlands.METHODS: We selected patients of 18 years and over, diagnosed between 2016 and 2017 with unresectable stage IIIC or IV melanoma, registered in the Dutch Melanoma Treatment Registry. To assess the association of BRAFV600-mutation status with OS we used the Cox proportional-hazards model.RESULTS: A total of 642 BRAFV600 wild-type and 853 mutant patients were included in the analysis. Median OS did not differ significantly between both groups, 15.2 months (95% confidence interval [CI]: 13.2-19.2) versus 20.6 months (95% CI: 18.3-25.0). Survival rates at 6 and 12 months were significantly lower for BRAFV600 wild-type patients compared with BRAFV600-mutant patients, 72.0% (95% CI: 68.6-75.6) and 56.0% (95% CI: 52.2-60.0) versus 83.4% (95% CI: 80.9-85.9) and 65.7% (95% CI: 62.6-69.0). Two-year survival was not significantly different between both groups, 41.1% (95% CI: 37.2-45.3) versus 47.0% (95% CI: 43.6-60.6). Between 0 and 10 months, BRAFV600 wild-type patients had a decreased survival with a hazard ratio for OS of 2.00 (95% CI: 1.62-2.46) but this effect disappeared after 10 months. At 12 months, BRAFV600-mutant patients had started with second-line systemic treatment more often compared with BRAFV600 wild-type patients (50% vs. 19%).CONCLUSION: These results suggest that advanced BRAFV600 wild-type melanoma patients have worse survival than BRAFV600-mutated patients during the first 10 months after diagnosis because of less available treatment options.

AB - OBJECTIVE: The aim of this study was to evaluate treatment patterns and overall survival (OS) of patients with BRAFV600 wild-type and BRAFV600-mutant advanced melanoma in the Netherlands.METHODS: We selected patients of 18 years and over, diagnosed between 2016 and 2017 with unresectable stage IIIC or IV melanoma, registered in the Dutch Melanoma Treatment Registry. To assess the association of BRAFV600-mutation status with OS we used the Cox proportional-hazards model.RESULTS: A total of 642 BRAFV600 wild-type and 853 mutant patients were included in the analysis. Median OS did not differ significantly between both groups, 15.2 months (95% confidence interval [CI]: 13.2-19.2) versus 20.6 months (95% CI: 18.3-25.0). Survival rates at 6 and 12 months were significantly lower for BRAFV600 wild-type patients compared with BRAFV600-mutant patients, 72.0% (95% CI: 68.6-75.6) and 56.0% (95% CI: 52.2-60.0) versus 83.4% (95% CI: 80.9-85.9) and 65.7% (95% CI: 62.6-69.0). Two-year survival was not significantly different between both groups, 41.1% (95% CI: 37.2-45.3) versus 47.0% (95% CI: 43.6-60.6). Between 0 and 10 months, BRAFV600 wild-type patients had a decreased survival with a hazard ratio for OS of 2.00 (95% CI: 1.62-2.46) but this effect disappeared after 10 months. At 12 months, BRAFV600-mutant patients had started with second-line systemic treatment more often compared with BRAFV600 wild-type patients (50% vs. 19%).CONCLUSION: These results suggest that advanced BRAFV600 wild-type melanoma patients have worse survival than BRAFV600-mutated patients during the first 10 months after diagnosis because of less available treatment options.

KW - BRAF mutation

KW - BRAF/MEK inhibitors

KW - CTLA-4 inhibitor

KW - National Registry

KW - advanced melanoma

KW - anti-PD-1-ligands

KW - checkpoint inhibitors

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U2 - 10.1097/COC.0000000000000786

DO - 10.1097/COC.0000000000000786

M3 - Article

C2 - 33332931

SN - 0277-3732

VL - 44

SP - 82

EP - 89

JO - American Journal of Clinical Oncology

JF - American Journal of Clinical Oncology

IS - 2

ER -

Nationwide Outcomes of Advanced Melanoma According to BRAFV600 Status

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Keywords

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