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
N1 - Funding Information:
This study was supported by the Dutch Melanoma Treatment Registry (DMTR); the Dutch Institute for Clinical Auditing foundation received a start-up 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 Sharp & Dohme, and Pierre Fabre. Roche Pharma stopped funding in 2019. Novartis stopped funding in 2023. Pierre Fabre started funding the DMTR in 2019. No funding was granted for this work.
Publisher Copyright:
© 2026 The Authors.
PY - 2026/6
Y1 - 2026/6
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
U2 - 10.1016/j.ejca.2026.116889
DO - 10.1016/j.ejca.2026.116889
M3 - Article
SN - 0959-8049
VL - 244
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 116889
ER -