Melanoma Management最新文献

The incidence of metastatic melanoma has been increasing dramatically over the last decades. Yet, there have been many new innovative therapies, such as targeted therapies and checkpoint inhibitors, which have made progress in survival for these patients. The oncology pharmacist is part of the healthcare team and can help in optimizing these newer therapies. There will be discussion about combination therapies, the oncology pharmacist's role, and issues at the core of his interest, such as drug interactions and complementary and alternative therapies.

Aim: Neoadjuvant treatment of locally advanced disease with BRAF inhibitors is expected to increase the likelihood of a R0 resection. We present six patients with stage III unresectable melanoma, neoadjuvantly treated with BRAF inhibitors.

Methods: Patients with unresectable, BRAF-mutated, stage III melanoma, were treated with BRAF inhibitors between 2012 and 2015. Unresectability was determined based on clinical and/or radiological findings. At maximal response, resection was performed. The specimen was reviewed to determine the degree of response.

Results: In five of six patients a radical resection was achieved. Postoperative complications were unremarkable. In five of six resected specimens, vital tumor tissue was found.

Conclusion: Neoadjuvant BRAF inhibitor treatment of locally advanced melanoma is feasible and has the potential to facilitate an R0 resection.

In vivo reflectance confocal microscopy (RCM) is a noninvasive high-resolution skin imaging tool that has become an important adjunct to clinical exam, dermoscopy and histopathology assessment, in the diagnosis and management of melanoma. RCM generates a horizontal view of the skin, whereby cellular and subcellular (e.g., nuclei, melanophages, collagen) structures, to the level of the upper dermis, are projected onto a screen at near-histological resolution. Morphologic descriptors, standardized terminology, and diagnostic algorithms are well established for the RCM assessment of melanoma, melanocytic, and nonmelanocytic lesions. Clinical applications of RCM in melanoma are broad and include diagnosis, assessment of large lesions on cosmetically sensitive areas, directing areas to biopsy, delineating margins prior to surgery, detecting response to treatment and assessing recurrence. This review will provide an overview of RCM technology, findings by melanoma subtype, clinical applications, as well as explore the accuracy of RCM for melanoma diagnosis, pitfalls and emerging uses of this technology ex vivo.

Aim: We aimed to characterize the safety profile of pembrolizumab in advanced melanoma patients at our center to better reflect 'real-world' data on anti-PD-1 inhibitors.

Materials & methods: At our institution, 58 ipilimumab-naive and 30 ipilimumab-treated patients with advanced melanoma who have received pembrolizumab between June 2014 and June 2017 were included for analysis.

Results: Incidence of any-grade and grade 3/4 toxicities were 81.8% (n = 72) and 12.5% (n = 11), respectively. The most common side effects were skin-related (61.4%, n = 54) and gastrointestinal-related (51.1%, n = 45) events. In total, 25% of patients required oral steroids to manage immune-related adverse events with a median cumulative prednisolone dose of 683 mg (range: 40-3745 mg).

Conclusion: Pembrolizumab is well tolerated in 'real-world' patients and severe toxicities can be effectively managed with systemic steroids.

Aim: We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients.

Methods: We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon.

Results: After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS.

Conclusion: Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.

Introduction: Immunotherapies, including checkpoint inhibitors (CIs) such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) inhibitors, are revolutionizing the treatment of advanced melanoma. Combining CTLA-4 and PD-1 inhibitors provides additional clinical benefit compared with single agents alone. However, combination therapy can increase the incidence of gastrointestinal adverse events (GI AEs). This systematic review assessed the epidemiological, clinical, economic, and humanistic burden of GI AEs due to combination CIs in advanced melanoma.

Methods: MEDLINE, EMBASE, and the Cochrane Library were systematically searched (December 2011 to December 2016) to identify primary studies, systematic reviews, meta-analyses, and conference proceedings (2014-2016) evaluating adults treated with ≥2 CIs for advanced melanoma.

Results: Of the 3391 identified articles, 14 were included. Most studies examined the ipilimumab plus nivolumab combination. Any grade and grade 3-4 GI AEs occurred in more patients receiving ipilimumab plus nivolumab versus ipilimumab or nivolumab alone. The most common grade 3-4 GI AEs were diarrhea and colitis. Grade 3-4 colitis occurred in more patients receiving ipilimumab plus nivolumab. However, grade 3-4 diarrhea occurred at the same rate as ipilimumab alone. GI AEs developed with ipilimumab plus nivolumab approximately 6.6 weeks after initiating treatment. No studies assessing the economic or humanistic burden of GI AEs were identified.

Conclusion: GI AEs occurred at a higher rate and greater severity in patients treated with ipilimumab plus nivolumab versus ipilimumab or nivolumab monotherapy. The lack of research on economic and humanistic burden of GI AEs with combination CIs for advanced melanoma represents an unmet need in the literature and should be explored in future studies.

Signal transduction inhibitors and anticheckpoint antibodies have significantly improved survival for metastatic melanoma patients, but most still die within 5 years. Vaccine approaches to induce immunity to well-characterized melanoma-associated antigens, or to antigens expressed on allogeneic tumor cell lines, have not resulted in approved agents. Despite the limitations associated with the immunosuppressive tumor microenvironment, there now is one intralesional autologous vaccine approved for patients who have primarily soft-tissue metastases. There is continued interest in patient-specific vaccines, especially dendritic cell vaccines that utilize ex vivo loading of autologous antigen, thus bypassing certain in vivo immunosuppressive cells and cytokines. Because of their mechanism of action and limited toxicity, they are potentially synergistic or additive to other antimelanoma therapies.