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.
Boreel et al. (Mon,) studied this question.