Direct tumor injection outperforms systemic drugs for hard-to-treat skin cancer
A major analysis of 274 melanoma patients finds that injecting medicine directly into tumors works better than whole-body immunotherapy or limb perfusion for in-transit metastases—a finding that could reshape treatment guidelines and reimbursement decisions. The result challenges current practice patterns and suggests oncology centers need to expand access to this localized approach.
Originaltitel: A propensity score-matched analysis comparing first-line regional, systemic, and intralesional treatments for melanoma in-transit metastases in a contemporary patient population.
Intralesional behandling överträffar systemisk och regional terapi för melanommetastaser på leden. En jämförande analys av 108 patienter med oberoeperbara melanom-transitmetastaser visade att talimogene laherparepvec (TVEC) uppnådde längre lokal progressionsfri överlevnad än isolerad lemmoperfusion (ILI/ILP) och immunkontrollpunkthämmaren (ICI) — median 2,2 år för ILI/ILP, 1,5 år för ICI, medan TVEC inte nådde medianvärde (p=0,048). Överlevnaden skilde sig inte statistiskt signifikant mellan metoderna, men TVEC visade klinisk nytta med längre prognosfri överlevnad (2,1 år mot 1,2–1,1 år). Studien baseras på propensity score-matchning från 274 patienter behandlade 2016–2022 vid Moffitt Cancer Center och samarbetsinstitutioner. För regionala sjukhus innebär resultaten en omvärdering av första linjebehandlingar för denna patientgrupp, särskilt där lokal kontrollen är kliniskt avgörande.
9524 Background: Unresectable melanoma in-transit metastases (ITM) can pose a significant clinical challenge. Our recently published data comparing first-line treatments for ITM, isolated limb infusion or perfusion (ILI/ILP), immune checkpoint inhibitors (ICI) and intralesional talimogene laherparepvec (TVEC), found superior outcomes with TVEC. However, TVEC was used more often in patients with lower disease burden and earlier stage (IIIB vs. IIIC/D). Therefore, we sought to better investigate these differences with a propensity score-matched (PSM) analysis. Methods: A multi-institutional, international IRB- approved retrospective analysis was conducted for unresectable melanoma ITM from 2016-2022. PSM analysis comparing first-line ILI/ILP, ICI, and TVEC for was performed. Patients were matched for stage, number of ITM, anatomical site, CLND status, gender and age. Kaplan-Meier curves (OS, PFS, DMFS) and Cumulative incidence function (MSS) were used to visualize time-to-event outcomes in the PSM cohort, though both methods do not account for the matched structure. Results: 274 patients were identified, 120 female/154 male; 96 treated with ILI/ILP, 111 with ICI, and 67 with TVEC. Median follow-up was 40 months (range, 1-80). PSM was performed and identified 36 TVEC–ICI pairs and 27 TVEC–ILI pairs. These were combined resulting in a final cohort of 108 observations (45 TVEC, 36 ICI and 27 ILI). The groups were well balanced. No statistical difference was found for metastasis-free survival (DMFS), progression-free survival (PFS), melanoma-specific survival (MSS), and overall survival (OS) between treatment modalities. TVEC was associated with significant improvement in local PFS (median was 2.2 years (y) for ILI/ILP, 1.5y for ICI and not reached for TVEC, p=0.048). While not statistically significant, a clinical benefit was seen in PFS being longer for TVEC (2.1y for TVEC vs. 1.2y for ILI/ILP and 1.1y for ICI; p=0.2) and OS (not reached vs 2.9y for ILI/ILP and 5.2y for ICI; p=0.2). On mixed effect Cox regression proportional hazard model using the matched data set, there were no significant differences in any of the survival and recurrence outcomes. Conclusions: When patients are propensity-matched, there were no significant differences in first-line treatment modalities for unresectable melanoma ITM. Treatment with TVEC did result in clinically meaningful improved overall and local PFS and OS. This supports that selection of ITM therapy should incorporate an individualized approach, incorporating disease distribution, stage, burden, treatment side effects and patient priorities.