Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy

Cato Boreel; Jessie de Ruijter; Olivier van Not; Manja Bloem; Lukas Been; Maureen Aarts; Franchette van den Berkmortel; Christian Blank; Marye Boers-Sonderen; Han Bonenkamp; Jan Willem de Groot; Dirk Grünhagen; John Haanen; M. Hilde Jalving; Djura Piersma; Bart Rikhof; Marion Stevense den Boer; Astrid van der Veldt; Lieke Simkens; Michel Wouters; Ellen Kapiteijn; Fons van den Eertwegh; Karijn Suijkerbuijk

doi:10.1016/j.ejca.2026.116889

Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy

Cato Boreel^*
, Jessie de Ruijter
, Olivier van Not
, Manja Bloem
, Lukas Been
, Maureen Aarts
, Franchette van den Berkmortel
, Christian Blank
, Marye Boers-Sonderen
, Han Bonenkamp
, Jan Willem de Groot
, Dirk Grünhagen
, John Haanen
, M. Hilde Jalving
, Djura Piersma
, Bart Rikhof
, Marion Stevense den Boer
, Astrid van der Veldt
, Lieke Simkens
, Michel Wouters

Ellen Kapiteijn, Fons van den Eertwegh, Karijn Suijkerbuijk

^*Corresponding author for this work

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

Abstract

Background Currently, no comprehensive overview exists of response and survival outcomes for first-line immune checkpoint inhibition, BRAF/BRAF + MEK inhibition (BRAF(/MEK)i), and talimogene laherparepvec (T-VEC) in melanoma patients with unresectable in-transit metastases (ITM). This study aims to provide a real-world overview of these outcomes. Methods Using data from the nationwide Dutch Melanoma Treatment Registry, all patients receiving systemic treatment from 2012 to July 2025 for unresectable ITM, with or without lymph node metastases (LNM) (stage III-IVM1a), were analysed for overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS). A multivariable Cox model adjusted for age, sex, ECOG PS, LDH, and LNM. Results In total, 530 patients were identified: 213 received first-line anti-PD1, 182 T-VEC, 67 BRAF(/MEK)i, 37 ipilimumab (IPI), and 31 ipilimumab + nivolumab (IPI+NIVO). Patients receiving T-VEC had more favorable baseline characteristics, including less often stage IV disease, less often LNM, and lower LDH. ORR were comparable between treatments: anti-PD1 53.1%, T-VEC 52.2%, BRAF(/MEK)i 62.7%. Median PFS was significantly shorter for T-VEC (5.6months; 95%CI 4.2–8.1) than for anti-PD1 (8.1months; 95%CI 5.9–13.8) and BRAF(/MEK)i (9.2months; 95%CI 6.9–14.3). Median OS favored T-VEC (not reached (NR); 95%CI 61.5-NR) over anti-PD1 (37.2months; 95%CI 32.3–64.7) and BRAF(/MEK)i (24.7months; 95%CI 18.0–62.1), but this difference between T-VEC and anti-PD1 disappeared after adjusting for confounders and no differences were observed in MSS. In the ITM-only subgroup, T-VEC-treated patients demonstrated longer observed OS than anti-PD1 and BRAF(/MEK)i, while in patients with ITM and LNM, anti-PD1 showed longer PFS but similar OS compared with T-VEC. Conclusions For ITM unresectable melanoma, first-line anti-PD1, T-VEC, and BRAF(/MEK)i can induce clinically meaningful and durable responses. The optimal treatment choice depends on patient and disease characteristics and preferences.

Original language	English
Article number	116889
Journal	European journal of cancer
Volume	244
Early online date	21 Jun 2026
DOIs	https://doi.org/10.1016/j.ejca.2026.116889
Publication status	Published - 26 Aug 2026

Keywords

BRAF/MEK inhibition
Immune checkpoint inhibitors
Immunotherapy
In-transit metastases
Regional therapy
Stage III-IV melanoma
T-VEC
Talimogene laherparepvec
Unresectable melanoma

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Boreel, C., de Ruijter, J., van Not, O., Bloem, M., Been, L., Aarts, M., van den Berkmortel, F., Blank, C., Boers-Sonderen, M., Bonenkamp, H., de Groot, J. W., Grünhagen, D., Haanen, J., Hilde Jalving, M., Piersma, D., Rikhof, B., Boer, M. S. D., van der Veldt, A., Simkens, L., ... Suijkerbuijk, K. (2026). Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy. European journal of cancer, 244, Article 116889. https://doi.org/10.1016/j.ejca.2026.116889

@article{3fcd80114d834bfe84953ab5127bfcd6,

title = "Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy",

abstract = "Background Currently, no comprehensive overview exists of response and survival outcomes for first-line immune checkpoint inhibition, BRAF/BRAF + MEK inhibition (BRAF(/MEK)i), and talimogene laherparepvec (T-VEC) in melanoma patients with unresectable in-transit metastases (ITM). This study aims to provide a real-world overview of these outcomes. Methods Using data from the nationwide Dutch Melanoma Treatment Registry, all patients receiving systemic treatment from 2012 to July 2025 for unresectable ITM, with or without lymph node metastases (LNM) (stage III-IVM1a), were analysed for overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS). A multivariable Cox model adjusted for age, sex, ECOG PS, LDH, and LNM. Results In total, 530 patients were identified: 213 received first-line anti-PD1, 182 T-VEC, 67 BRAF(/MEK)i, 37 ipilimumab (IPI), and 31 ipilimumab + nivolumab (IPI+NIVO). Patients receiving T-VEC had more favorable baseline characteristics, including less often stage IV disease, less often LNM, and lower LDH. ORR were comparable between treatments: anti-PD1 53.1\%, T-VEC 52.2\%, BRAF(/MEK)i 62.7\%. Median PFS was significantly shorter for T-VEC (5.6months; 95\%CI 4.2{\textendash}8.1) than for anti-PD1 (8.1months; 95\%CI 5.9{\textendash}13.8) and BRAF(/MEK)i (9.2months; 95\%CI 6.9{\textendash}14.3). Median OS favored T-VEC (not reached (NR); 95\%CI 61.5-NR) over anti-PD1 (37.2months; 95\%CI 32.3{\textendash}64.7) and BRAF(/MEK)i (24.7months; 95\%CI 18.0{\textendash}62.1), but this difference between T-VEC and anti-PD1 disappeared after adjusting for confounders and no differences were observed in MSS. In the ITM-only subgroup, T-VEC-treated patients demonstrated longer observed OS than anti-PD1 and BRAF(/MEK)i, while in patients with ITM and LNM, anti-PD1 showed longer PFS but similar OS compared with T-VEC. Conclusions For ITM unresectable melanoma, first-line anti-PD1, T-VEC, and BRAF(/MEK)i can induce clinically meaningful and durable responses. The optimal treatment choice depends on patient and disease characteristics and preferences.",

keywords = "BRAF/MEK inhibition, Immune checkpoint inhibitors, Immunotherapy, In-transit metastases, Regional therapy, Stage III-IV melanoma, T-VEC, Talimogene laherparepvec, Unresectable melanoma",

author = "Cato Boreel and \{de Ruijter\}, Jessie and \{van Not\}, Olivier and Manja Bloem and Lukas Been and Maureen Aarts and \{van den Berkmortel\}, Franchette and Christian Blank and Marye Boers-Sonderen and Han Bonenkamp and \{de Groot\}, \{Jan Willem\} and Dirk Gr{\"u}nhagen and John Haanen and \{Hilde Jalving\}, M. and Djura Piersma and Bart Rikhof and Boer, \{Marion Stevense den\} and \{van der Veldt\}, Astrid and Lieke Simkens and Michel Wouters and Ellen Kapiteijn and \{van den Eertwegh\}, Fons and Karijn Suijkerbuijk",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors.",

year = "2026",

month = aug,

day = "26",

doi = "10.1016/j.ejca.2026.116889",

language = "English",

volume = "244",

journal = "European journal of cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Boreel, C, de Ruijter, J, van Not, O, Bloem, M, Been, L, Aarts, M, van den Berkmortel, F, Blank, C, Boers-Sonderen, M, Bonenkamp, H, de Groot, JW, Grünhagen, D, Haanen, J, Hilde Jalving, M, Piersma, D, Rikhof, B, Boer, MSD, van der Veldt, A, Simkens, L, Wouters, M, Kapiteijn, E, van den Eertwegh, F & Suijkerbuijk, K 2026, 'Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy', European journal of cancer, vol. 244, 116889. https://doi.org/10.1016/j.ejca.2026.116889

TY - JOUR

T1 - Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy

AU - Boreel, Cato

AU - de Ruijter, Jessie

AU - van Not, Olivier

AU - Bloem, Manja

AU - Been, Lukas

AU - Aarts, Maureen

AU - van den Berkmortel, Franchette

AU - Blank, Christian

AU - Boers-Sonderen, Marye

AU - Bonenkamp, Han

AU - de Groot, Jan Willem

AU - Grünhagen, Dirk

AU - Haanen, John

AU - Hilde Jalving, M.

AU - Piersma, Djura

AU - Rikhof, Bart

AU - Boer, Marion Stevense den

AU - van der Veldt, Astrid

AU - Simkens, Lieke

AU - Wouters, Michel

AU - Kapiteijn, Ellen

AU - van den Eertwegh, Fons

AU - Suijkerbuijk, Karijn

PY - 2026/8/26

Y1 - 2026/8/26

N2 - Background Currently, no comprehensive overview exists of response and survival outcomes for first-line immune checkpoint inhibition, BRAF/BRAF + MEK inhibition (BRAF(/MEK)i), and talimogene laherparepvec (T-VEC) in melanoma patients with unresectable in-transit metastases (ITM). This study aims to provide a real-world overview of these outcomes. Methods Using data from the nationwide Dutch Melanoma Treatment Registry, all patients receiving systemic treatment from 2012 to July 2025 for unresectable ITM, with or without lymph node metastases (LNM) (stage III-IVM1a), were analysed for overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS). A multivariable Cox model adjusted for age, sex, ECOG PS, LDH, and LNM. Results In total, 530 patients were identified: 213 received first-line anti-PD1, 182 T-VEC, 67 BRAF(/MEK)i, 37 ipilimumab (IPI), and 31 ipilimumab + nivolumab (IPI+NIVO). Patients receiving T-VEC had more favorable baseline characteristics, including less often stage IV disease, less often LNM, and lower LDH. ORR were comparable between treatments: anti-PD1 53.1%, T-VEC 52.2%, BRAF(/MEK)i 62.7%. Median PFS was significantly shorter for T-VEC (5.6months; 95%CI 4.2–8.1) than for anti-PD1 (8.1months; 95%CI 5.9–13.8) and BRAF(/MEK)i (9.2months; 95%CI 6.9–14.3). Median OS favored T-VEC (not reached (NR); 95%CI 61.5-NR) over anti-PD1 (37.2months; 95%CI 32.3–64.7) and BRAF(/MEK)i (24.7months; 95%CI 18.0–62.1), but this difference between T-VEC and anti-PD1 disappeared after adjusting for confounders and no differences were observed in MSS. In the ITM-only subgroup, T-VEC-treated patients demonstrated longer observed OS than anti-PD1 and BRAF(/MEK)i, while in patients with ITM and LNM, anti-PD1 showed longer PFS but similar OS compared with T-VEC. Conclusions For ITM unresectable melanoma, first-line anti-PD1, T-VEC, and BRAF(/MEK)i can induce clinically meaningful and durable responses. The optimal treatment choice depends on patient and disease characteristics and preferences.

AB - Background Currently, no comprehensive overview exists of response and survival outcomes for first-line immune checkpoint inhibition, BRAF/BRAF + MEK inhibition (BRAF(/MEK)i), and talimogene laherparepvec (T-VEC) in melanoma patients with unresectable in-transit metastases (ITM). This study aims to provide a real-world overview of these outcomes. Methods Using data from the nationwide Dutch Melanoma Treatment Registry, all patients receiving systemic treatment from 2012 to July 2025 for unresectable ITM, with or without lymph node metastases (LNM) (stage III-IVM1a), were analysed for overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS). A multivariable Cox model adjusted for age, sex, ECOG PS, LDH, and LNM. Results In total, 530 patients were identified: 213 received first-line anti-PD1, 182 T-VEC, 67 BRAF(/MEK)i, 37 ipilimumab (IPI), and 31 ipilimumab + nivolumab (IPI+NIVO). Patients receiving T-VEC had more favorable baseline characteristics, including less often stage IV disease, less often LNM, and lower LDH. ORR were comparable between treatments: anti-PD1 53.1%, T-VEC 52.2%, BRAF(/MEK)i 62.7%. Median PFS was significantly shorter for T-VEC (5.6months; 95%CI 4.2–8.1) than for anti-PD1 (8.1months; 95%CI 5.9–13.8) and BRAF(/MEK)i (9.2months; 95%CI 6.9–14.3). Median OS favored T-VEC (not reached (NR); 95%CI 61.5-NR) over anti-PD1 (37.2months; 95%CI 32.3–64.7) and BRAF(/MEK)i (24.7months; 95%CI 18.0–62.1), but this difference between T-VEC and anti-PD1 disappeared after adjusting for confounders and no differences were observed in MSS. In the ITM-only subgroup, T-VEC-treated patients demonstrated longer observed OS than anti-PD1 and BRAF(/MEK)i, while in patients with ITM and LNM, anti-PD1 showed longer PFS but similar OS compared with T-VEC. Conclusions For ITM unresectable melanoma, first-line anti-PD1, T-VEC, and BRAF(/MEK)i can induce clinically meaningful and durable responses. The optimal treatment choice depends on patient and disease characteristics and preferences.

KW - BRAF/MEK inhibition

KW - Immune checkpoint inhibitors

KW - Immunotherapy

KW - In-transit metastases

KW - Regional therapy

KW - Stage III-IV melanoma

KW - T-VEC

KW - Talimogene laherparepvec

KW - Unresectable melanoma

UR - https://www.scopus.com/pages/publications/105042535875

U2 - 10.1016/j.ejca.2026.116889

DO - 10.1016/j.ejca.2026.116889

M3 - Article

AN - SCOPUS:105042535875

SN - 0959-8049

VL - 244

JO - European journal of cancer

JF - European journal of cancer

M1 - 116889

ER -

Response and survival in unresectable in-transit metastatic melanoma according to treatment strategy

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Keywords

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