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

Cato Boreel1, Jessie de Ruijter2, Olivier van Not3

  • 1Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Medical Oncology, University Medical Centre Utrecht, Utrecht University, Heidelberglaan 100, Utrecht 3584CX, the Netherlands.

European Journal of Cancer (Oxford, England : 1990)
|June 23, 2026
PubMed
Abstract

Insights

First-line treatments like anti-PD1, talimogene laherparepvec (T-VEC), and BRAF/BRAF+MEK inhibition show comparable response rates for unresectable melanoma with in-transit metastases (ITM). Treatment choice depends on individual patient and disease factors for optimal outcomes.

Area of Science:

  • Oncology
  • Immunotherapy
  • Melanoma Research

Background:

  • Limited real-world data exists for first-line treatments in unresectable in-transit melanoma (ITM).
  • Key treatments include immune checkpoint inhibitors (anti-PD1), BRAF/BRAF+MEK inhibition (BRAF(/MEK)i), and talimogene laherparepvec (T-VEC).

Purpose of the Study:

  • To provide a comprehensive overview of response and survival outcomes for first-line systemic therapies in unresectable ITM patients.
  • To compare the efficacy of anti-PD1, T-VEC, and BRAF(/MEK)i in a real-world setting.

Main Methods:

  • Analysis of the nationwide Dutch Melanoma Treatment Registry (2012-2025).
  • Inclusion of patients with unresectable ITM (stage III-IVM1a), with or without lymph node metastases (LNM).
  • Evaluation of overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) using multivariable Cox models.

Main Results:

  • 530 patients received first-line anti-PD1 (n=213), T-VEC (n=182), BRAF(/MEK)i (n=67), ipilimumab (n=37), or ipilimumab+nivolumab (n=31).
  • ORR was comparable across anti-PD1 (53.1%), T-VEC (52.2%), and BRAF(/MEK)i (62.7%).
  • Median PFS was shorter for T-VEC (5.6 months) versus anti-PD1 (8.1 months) and BRAF(/MEK)i (9.2 months). Median OS favored T-VEC (NR) over anti-PD1 (37.2 months) and BRAF(/MEK)i (24.7 months), but differences diminished after adjusting for confounders.

Conclusions:

  • First-line anti-PD1, T-VEC, and BRAF(/MEK)i offer clinically meaningful and durable responses in unresectable ITM melanoma.
  • Optimal treatment selection requires consideration of patient-specific and disease characteristics.
  • Real-world data supports the efficacy of these novel therapies in advanced melanoma.
Keywords:
BRAF/MEK inhibitionImmune checkpoint inhibitorsImmunotherapyIn-transit metastasesRegional therapyStage III-IV melanomaT-VECTalimogene laherparepvecUnresectable melanoma

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