Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Isabella A J van Duin; Sjoerd G Elias; Alfonsus J M van den Eertwegh; Jan Willem B de Groot; Willeke A M Blokx; Paul J van Diest; Tim Leiner; Joost J C Verhoeff; Rik J Verheijden; Olivier J van Not; Maureen J B Aarts; Franchette W P J van den Berkmortel; Christian U Blank; John B A G Haanen; Geke A P Hospers; Anna M Kamphuis; Djura Piersma; Rozemarijn S van Rijn; Astrid A M van der Veldt; Gerard Vreugdenhil; Michel W J M Wouters; Marion A M Stevense-den Boer; Marye J Boers-Sonderen; Ellen Kapiteijn; Karijn P M Suijkerbuijk

doi:10.1002/ijc.34479

Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Isabella A J van Duin^*, Sjoerd G Elias, Alfonsus J M van den Eertwegh, Jan Willem B de Groot, Willeke A M Blokx, Paul J van Diest, Tim Leiner, Joost J C Verhoeff, Rik J Verheijden, Olivier J van Not, Maureen J B Aarts, Franchette W P J van den Berkmortel, Christian U Blank, John B A G Haanen, Geke A P Hospers, Anna M Kamphuis, Djura Piersma, Rozemarijn S van Rijn, Astrid A M van der Veldt, Gerard VreugdenhilMichel W J M Wouters, Marion A M Stevense-den Boer, Marye J Boers-Sonderen, Ellen Kapiteijn, Karijn P M Suijkerbuijk

^*Corresponding author for this work

Radiology & Nuclear Medicine

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Abstract

Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

Original language	English
Pages (from-to)	2493-2502
Number of pages	10
Journal	International Journal of Cancer
Volume	152
Issue number	12
Early online date	26 Feb 2023
DOIs	https://doi.org/10.1002/ijc.34479
Publication status	Published - 15 Jun 2023

Bibliographical note

FUNDING INFORMATION:
For this work, no funding was granted. For the Dutch Melanoma
Treatment Registry (DMTR), the Dutch Institute for Clinical
Auditing foundation received a start-up grant from 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 the
DMTR in 2019.

Publisher Copyright:
© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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van Duin, I. A. J., Elias, S. G., van den Eertwegh, A. J. M., de Groot, J. W. B., Blokx, W. A. M., van Diest, P. J., Leiner, T., Verhoeff, J. J. C., Verheijden, R. J., van Not, O. J., Aarts, M. J. B., van den Berkmortel, F. W. P. J., Blank, C. U., Haanen, J. B. A. G., Hospers, G. A. P., Kamphuis, A. M., Piersma, D., van Rijn, R. S., van der Veldt, A. A. M., ... Suijkerbuijk, K. P. M. (2023). Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma. International Journal of Cancer, 152(12), 2493-2502. https://doi.org/10.1002/ijc.34479

@article{ac4bac2d34004332aa9794157d7017be,

title = "Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma",

abstract = "Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.",

author = "{van Duin}, {Isabella A J} and Elias, {Sjoerd G} and {van den Eertwegh}, {Alfonsus J M} and {de Groot}, {Jan Willem B} and Blokx, {Willeke A M} and {van Diest}, {Paul J} and Tim Leiner and Verhoeff, {Joost J C} and Verheijden, {Rik J} and {van Not}, {Olivier J} and Aarts, {Maureen J B} and {van den Berkmortel}, {Franchette W P J} and Blank, {Christian U} and Haanen, {John B A G} and Hospers, {Geke A P} and Kamphuis, {Anna M} and Djura Piersma and {van Rijn}, {Rozemarijn S} and {van der Veldt}, {Astrid A M} and Gerard Vreugdenhil and Wouters, {Michel W J M} and {Stevense-den Boer}, {Marion A M} and Boers-Sonderen, {Marye J} and Ellen Kapiteijn and Suijkerbuijk, {Karijn P M}",

note = "FUNDING INFORMATION: For this work, no funding was granted. For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from 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 the DMTR in 2019. Publisher Copyright: {\textcopyright} 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",

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doi = "10.1002/ijc.34479",

language = "English",

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van Duin, IAJ, Elias, SG, van den Eertwegh, AJM, de Groot, JWB, Blokx, WAM, van Diest, PJ, Leiner, T, Verhoeff, JJC, Verheijden, RJ, van Not, OJ, Aarts, MJB, van den Berkmortel, FWPJ, Blank, CU, Haanen, JBAG, Hospers, GAP, Kamphuis, AM, Piersma, D, van Rijn, RS, van der Veldt, AAM, Vreugdenhil, G, Wouters, MWJM, Stevense-den Boer, MAM, Boers-Sonderen, MJ, Kapiteijn, E & Suijkerbuijk, KPM 2023, 'Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma', International Journal of Cancer, vol. 152, no. 12, pp. 2493-2502. https://doi.org/10.1002/ijc.34479

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T1 - Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

AU - van Duin, Isabella A J

AU - Elias, Sjoerd G

AU - van den Eertwegh, Alfonsus J M

AU - de Groot, Jan Willem B

AU - Blokx, Willeke A M

AU - van Diest, Paul J

AU - Leiner, Tim

AU - Verhoeff, Joost J C

AU - Verheijden, Rik J

AU - van Not, Olivier J

AU - Aarts, Maureen J B

AU - van den Berkmortel, Franchette W P J

AU - Blank, Christian U

AU - Haanen, John B A G

AU - Hospers, Geke A P

AU - Kamphuis, Anna M

AU - Piersma, Djura

AU - van Rijn, Rozemarijn S

AU - van der Veldt, Astrid A M

AU - Vreugdenhil, Gerard

AU - Wouters, Michel W J M

AU - Stevense-den Boer, Marion A M

AU - Boers-Sonderen, Marye J

AU - Kapiteijn, Ellen

AU - Suijkerbuijk, Karijn P M

N1 - FUNDING INFORMATION: For this work, no funding was granted. For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from 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 the DMTR in 2019. Publisher Copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2023/6/15

Y1 - 2023/6/15

N2 - Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

AB - Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance. We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing first-line systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years). Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

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DO - 10.1002/ijc.34479

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EP - 2502

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 12

ER -

Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

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