Five-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma.
Abstract Background In the previously reported primary analyses of this phase 3 trial, 12 months of adjuvant pembrolizumab resulted in significantly longer recurrence- and distant metastasis-free survival than placebo in patients with resected high-risk stage III melanoma. To confirm the stability of these benefits, longer-term data were needed. Methods We randomly assigned 1019 patients to receive 200 mg of pembrolizumab or placebo intravenously every 3 weeks for a total of 18 doses (approximately 1 year) and had previously reported data with a 15-, 36-, and 42-month median follow-up. We now report data at a median follow-up of 4.9 years. [...]
Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection.
Abstract Abstract Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up [...]
Neoadjuvant nivolumab + T-VEC combination therapy for resectable early stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: study protocol of the NIVEC trial.
Abstract Background: Trials investigating neoadjuvant treatment with immune checkpoint inhibitors (ICI) in patients with melanoma have shown high clinical and pathologic response rates. Treatment with talimogene laherparepvec (T-VEC), a modified herpes simplex virus type-1 (HSV-1), is approved for patients with unresectable stage IIIB-IVM1a melanoma and has the potential to make tumors more susceptible for ICI. Combination ICI and intralesional T-VEC has already been investigated in patients with unresectable stage IIIB-IV disease, however, no data is available yet on the potential benefit of this combination therapy in neoadjuvant setting. Methods: This single center, single arm, phase II study aims to show an [...]
Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.
Abstract Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, setting, and participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 [...]
Diagnosis and treatment of Merkel cell carcinoma: European consensus-based interdisciplinary guideline – Update 2022.
Abstract Merkel cell carcinoma (MCC) is a rare skin cancer, accounting for less than 1% of all cutaneous malignancies. It is found predominantly in white populations and risk factors include advanced age, ultraviolet exposure, male sex, immunosuppression, such as AIDS/HIV infection, haematological malignancies or solid organ transplantation, and Merkel cell polyomavirus infection. MCC is an aggressive tumour with 26% of cases presenting lymph node involvement at diagnosis and 8% with distant metastases. Five-year overall survival rates range between 48% and 63%. Two subsets of MCC have been characterised with distinct molecular pathogenetic pathways: ultraviolet-induced MCC versus virus-positive MCC, which [...]
Neoadjuvant Immune Checkpoint Inhibitor Therapy in Melanoma: Efficacy, Safety and Timing
Abstract The introduction of effective systemic therapies has significantly changed the treatment of stage III and IV melanoma. Both immune checkpoint inhibitors and targeted therapies have improved recurrence-free survival in the adjuvant setting. Recent interest has sparked for neoadjuvant systemic therapy with immune checkpoint inhibitors. The intended benefit of pre-operative treatment with immunotherapy is amongst others to enable tailoring of the surgery and adjuvant systemic therapy according to the treatment response. Most importantly, recurrence-free survival might be improved by neoadjuvant systemic therapy over the current standard of care of surgery followed by adjuvant systemic therapy. The first phase I [...]
Representativeness of the Index Lymph Node for Total Nodal Basin in Pathologic Response Assessment After Neoadjuvant Checkpoint Inhibitor Therapy in Patients With Stage III Melanoma
Abstract Importance: Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (n = 12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen. Objective: To assess the concordance of response between the ILN and the total lymph node bed in [...]
Prognostic and predictive value of β-blockers in the EORTC 1325/KEYNOTE-054 phase III trial of pembrolizumab versus placebo in resected high-risk stage III melanoma
Abstract Background: β-adrenergic receptors are upregulated in melanoma cells and contribute to an immunosuppressive, pro-tumorigenic microenvironment. This study investigated the prognostic and predictive value of β-adrenoreceptor blockade by β-blockers in the EORTC1325/KEYNOTE-054 randomised controlled trial. Methods: Patients with resected stage IIIA, IIIB or IIIC melanoma and regional lymphadenectomy received 200 mg of adjuvant pembrolizumab (n = 514) or placebo (n = 505) every three weeks for one year or until recurrence or unacceptable toxicity. At a median follow-up of 3 years, pembrolizumab prolonged recurrence-free survival (RFS) compared to placebo (hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.47-0.68). β-blocker use was [...]
Merkel Cell Carcinoma, the Impact of Clinical Excision Margins and Mohs Micrographic Surgery on Recurrence and Survival: A Systematic Review
Abstract Background: When treating Merkel cell carcinoma (MCC), the relation between wide local excision (WLE) margin and recurrence or survival is unclear. Mohs micrographic surgery (MMS) is an alternative surgical option for MCC, but it is unknown whether the local recurrence rate differs between MMS and WLE. Objective: To systematically assess the available literature to determine the recurrence and survival rates when treating MCC with MMS and different clinical excision margins. Materials and methods: The MEDLINE, EMBASE, and CENTRAL databases were searched. Two independent reviewers selected studies that defined clear excision margins and either recurrence or survival. When possible, individual cases were [...]
Representativeness of the Index Lymph Node for Total Nodal Basin in Pathologic Response Assessment After Neoadjuvant Checkpoint Inhibitor Therapy in Patients With Stage III Melanoma
Abstract Importance: Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection (TLND) can be safely omitted when a major pathologic response in the largest lymph node metastasis at baseline (index lymph node; ILN) is obtained is currently being investigated. A previous small pilot study (n = 12) showed that the response in the ILN may be representative of the pathologic response in the entire TLND specimen. Objective: To assess the concordance of response between the ILN and the total lymph node bed in [...]