Relapse-free survival with adjuvant dabrafenib/trametinib therapy after relapse on a prior adjuvant CPI in BRAF V600-mutated stage III/IV melanoma.
Abstract Background: In BRAF-mutated high-risk melanoma, targeted therapy (BRAF/MEK inhibitors) and checkpoint inhibitor (CPI) immunotherapy have durable benefits as first-line (1L) adjuvant therapy. Based on differing action mechanisms of BRAF/MEK inhibitors and CPI immunotherapies, there is interest in evaluating the activity of 2L adjuvant targeted therapy in decreasing the risk of subsequent recurrence after repeat resection following relapse on/after 1L adjuvant CPI. Patients and methods: This was a retrospective review of BRAF V600-mutated resected stage III/IV melanoma patients in the United States, Australia, and The Netherlands who received 1L adjuvant CPI immunotherapy, relapsed locoregionally/distantly, were again resected to no evidence of [...]
Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.
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A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases
Abstract Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest [...]
A comparison of isolated limb infusion/perfusion, immune checkpoint inhibitors, and intralesional therapy as first-line treatment for patients with melanoma in-transit metastases
Abstract Background: Isolated limb infusion and perfusion (ILI/ILP) has been a mainstay treatment for unresectable melanoma in-transit metastases (ITM), but increased use of immune checkpoint inhibitors (ICI) and intralesional therapy (talimogene laherparepvec [TVEC]) introduced several different management options. This study compares first-line ILI/ILP, ICI, and TVEC. Methods: Retrospective review from 12 international institutions included patients treated from 1990 to 2022 with first-line ILI/ILP, ICI, or TVEC for unresectable melanoma ITM. Results: A total of 551 patients were treated, with ILI/ILP (n = 356), ICI (n = 125), and TVEC (n = 70) with median follow-up of 5.5 years. Tumor burden was highest [...]
Seven-year analysis of adjuvant pembrolizumab versus placebo in stage III melanoma in the EORTC1325 / KEYNOTE-054 trial.
Abstract In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) than placebo in patients with resected high risk stage III melanoma. Stability of these benefits when the median follow-up was 3.5 and 5 years was published. Here we report results with a longer follow-up. Methods: We randomized 1019 patients to receive pembrolizumab 200 mg or placebo, intravenously every 3 weeks for a total of 18 doses. RFS in the overall population and in the subgroup of patients with melanoma positive for [...]
1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma
Background The interferon gamma gene signature (IFNg) has been shown to be predictive and prognostic in patients (pts) with macroscopic stage III or IV melanoma. In macroscopic stage III melanoma, IFNg from lymph node biopsies (LN-IFNg) might be used in the future for neoadjuvant treatment decisions (combination vs monotherapy). To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts. [...]
LBA41 Long-term survival with neoadjuvant therapy in melanoma: Updated pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC)
Background Neoadjuvant therapy is the standard of care for resectable stage ≥IIIB melanoma. In 2021, the International Neoadjuvant Melanoma Consortium published a pooled analysis of 196 melanoma pts treated with neoadjuvant immunotherapy (ICI) or BRAF/MEK targeted therapy. Here, we provide a survival update of an expanded cohort. Methods Clinical, radiographic, histopathological, and survival data were collated for pts with resectable stage ≥IIIB melanoma who received neoadjuvant therapy in a clinical trial or routine care. Outcomes included major pathological response (MPR) rate, event-free survival (EFS; progression prior to surgery, recurrence post-surgery or death), and recurrence-free survival (RFS). Results Data was [...]
Reply to: Pioneering combination: Nivolumab and isolated limb perfusion in melanoma in-transit metastases treatment.
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Comparison of clinicopathological features and treatment outcomes for cutaneous melanomas of the head and neck and melanomas arising at other sites: Implications for systemic therapy.
Abstract Background: Melanoma is increasingly recognized as a heterogeneous disease, with conflicting evidence regarding whether cutaneous head and neck melanoma (CHNM) represents a distinct entity. Objective: Comparison of clinicopathological features and treatment outcomes of CHNM and cutaneous melanomas of other sites (CMOS). Methods: Patients with CHNM and CMOS diagnosed between 2000 and 2018 were included. Locoregional control, distant metastasis-free survival, melanoma-specific survival (MSS), and overall survival (OS) were described using the Kaplan-Meier method. Cox regression analyses were performed to examine associations between prognostic factors and outcomes. Additional analyses of survival from time of stage IV disease diagnosis were undertaken, stratified by receipt [...]
The Effect of Neoadjuvant Systemic Therapy on Surgical Outcomes After Lymph Node Dissections for Stage III Melanoma; An Australian Cohort
Abstract Background: Neoadjuvant systemic therapy (NAST) for patients with stage III melanoma achieves high major pathologic response rates and high recurrence-free survival rates. This study aimed to determine how NAST with targeted therapies (TTs) and immune checkpoint inhibitors (ICIs) influences surgical outcomes after lymph node dissection in terms of complications, morbidity, and textbook outcomes. Methods: Patients who underwent a lymph node dissection after either NAST in a clinical trial or upfront surgery for stage III melanoma between 2014 and 2022 were identified from an institutional research database. Results: The study included 89 NAST-treated patients and 79 upfront surgery-treated patients. The rate of [...]