Melanoma Management最新文献

{"title":"Continuing and new roles for surgery in the management of patients with stage IV melanoma.","authors":"Erica B Friedman, John F Thompson","doi":"10.2217/mmt-2017-0024","DOIUrl":"https://doi.org/10.2217/mmt-2017-0024","url":null,"abstract":"Until a few years ago, it was generally agreed that the best treatment option for melanoma patients with distant metastases (stage IV disease) was complete surgical resection, whenever possible. Those with more widespread disease or who were deemed unfit for surgery were referred to medical oncologists, but they had little to offer in the way of effective systemic therapy, and often simply recommended palliative end-of-life care. In the second decade of the 21st century, however, we have witnessed a dramatic change in the management of metastatic melanoma, with the introduction of two novel therapeutic drug classes – targeted small molecule inhibitors of the oncogenic BRAF V600 mutation or a downstream signaling target (MEK), and immune checkpoint inhibitors consisting of monoclonal antibodies against CTLA-4 and PD-1. Accordingly, clinical decision making for patients with stage IV melanoma has become increasingly complex, and multiple clinical trials are in progress to determine the best strategies to combine or sequence systemic treatment and surgery. Some believe that a complete paradigm shift in the approach to patients with metastatic melanoma has occurred, with surgeons no longer playing any useful role. A more enlightened view is that we have entered an era of truly integrated and carefully coordinated multidisciplinary care of these patients. The reality is that surgery remains an excellent treatment option for patients with just one or a small number of distant metastases. Complete surgical resection offers a rapid, cost-effective means of rendering them clinically disease free and should be the first-line treatment in appropriately screened patients. This strategy is supported by the results of several clinical trials. Good survival outcomes were achieved in the CanvaxinTM stage IV trial, which compared patients who received adjuvant treatment with Bacillus Calmette–Guérin (BCG) and an allogenic melanoma vaccine after complete resection of metastatic disease to patients who received only BCG with placebo after resection [1]. While the study did not show any benefit in the vaccine-treated arm, 5-year overall survival (OS) rates following complete surgical resection were approximately 40% in both groups, substantially higher than would have been expected if the patients had been treated with the systemic therapies that were available at the time. The Southwestern Oncology Group’s prospective multicenter trial of patients with surgically resectable metastatic melanoma also found that prolonged OS can be achieved by complete resection. While median relapse-free survival (RFS) was short (5 months), median OS was 21 months and 4-year survival was 31% [2]. In the first Multicenter Lymphadenectomy Trial, retrospective analysis of patients who developed distant metastases found that inclusion of surgery as part of the treatment plan conferred a survival advantage, even in patients who developed high-risk visceral metastases. If surgery was perfo","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"5 1","pages":"MMT03"},"PeriodicalIF":3.6,"publicationDate":"2018-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon is associated with improved survival for node-positive cutaneous melanoma: a single-institution experience.","authors":"Daniel E Oliver,&nbsp;Vernon K Sondak,&nbsp;Tobin Strom,&nbsp;Jonathan S Zager,&nbsp;Arash O Naghavi,&nbsp;Amod Sarnaik,&nbsp;Jane L Messina,&nbsp;Jimmy J Caudell,&nbsp;Andy M Trotti,&nbsp;Javier F Torres-Roca,&nbsp;Nikhil I Khushalani,&nbsp;Louis B Harrison","doi":"10.2217/mmt-2017-0025","DOIUrl":"https://doi.org/10.2217/mmt-2017-0025","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"5 1","pages":"MMT02"},"PeriodicalIF":3.6,"publicationDate":"2018-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal adverse events with combination of checkpoint inhibitors in advanced melanoma: a systematic review.","authors":"Elizabeth S Mearns,&nbsp;Jill A Bell,&nbsp;Aaron Galaznik,&nbsp;Stefanie M Puglielli,&nbsp;Allie B Cichewicz,&nbsp;Talia Boulanger,&nbsp;Ignacio Garcia-Ribas","doi":"10.2217/mmt-2017-0027","DOIUrl":"10.2217/mmt-2017-0027","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"5 1","pages":"MMT01"},"PeriodicalIF":3.6,"publicationDate":"2018-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update on the relevance of vaccine research for the treatment of metastatic melanoma.","authors":"Robert O Dillman","doi":"10.2217/mmt-2017-0021","DOIUrl":"10.2217/mmt-2017-0021","url":null,"abstract":"<p><p>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 <i>ex vivo</i> loading of autologous antigen, thus bypassing certain <i>in vivo</i> immunosuppressive cells and cytokines. Because of their mechanism of action and limited toxicity, they are potentially synergistic or additive to other antimelanoma therapies.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"203-215"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Has the melanoma information tsunami become a maelstrom?","authors":"John F Thompson, Alexander M Menzies","doi":"10.2217/mmt-2017-0020","DOIUrl":"10.2217/mmt-2017-0020","url":null,"abstract":"","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"179-182"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094604/pdf/mmt-04-179.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of the cutaneous adverse effects of antimelanoma therapy.","authors":"Rose Congwei Liu,&nbsp;Germana Consuegra,&nbsp;Pablo Fernández-Peñas","doi":"10.2217/mmt-2017-0015","DOIUrl":"https://doi.org/10.2217/mmt-2017-0015","url":null,"abstract":"The advent of targeted therapy and immunotherapy has revolutionized the management of advanced melanoma. However, these novel therapies are associated with adverse effects (AEs), of which cutaneous toxicities are the most frequently observed. These cutaneous AEs can exert significant morbidity and impact on patient quality of life, hence the recognition and management of AEs is fundamental in preventing interruption or cessation of survival-prolonging treatments. Additionally, knowledge of these AEs are necessary in order for healthcare professionals to counsel patients when starting treatment and in the initiation of AE prophylaxis. The incidence and clinical presentation of the cutaneous toxicities of novel melanoma therapies will be discussed, and treatment guidelines provided.","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"187-202"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36471132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic molecular testing in melanoma: ready for prime time?","authors":"Jennifer Keller,&nbsp;Laurence P Diggs,&nbsp;Eddy C Hsueh","doi":"10.2217/mmt-2017-0013","DOIUrl":"https://doi.org/10.2217/mmt-2017-0013","url":null,"abstract":"","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"171-174"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36470686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-PD-1 and PD-L1 antibodies in metastatic melanoma.","authors":"Ester Simeone,&nbsp;Paolo A Ascierto","doi":"10.2217/mmt-2017-0018","DOIUrl":"https://doi.org/10.2217/mmt-2017-0018","url":null,"abstract":"“ Genetic mutations and dysregulation of the immune system may be related in some patients and may have an important impact on the efficacy of therapies. ” The advent of monoclonal antibodies that target CTLA-4 (ipilimumab) or PD-1 checkpoints (nivolumab and pembrolizumab) has increased hopes of improved outcomes in advanced melanoma. However, resistance remains an important issue. Genetic mutations and dysregulation of the immune system may be related in some patients and may have an important impact on the efficacy of therapies. Another explanation may be that patients who progressed in the chemotherapy arm may then have received pembrolizumab. In the CheckMate 066 study in patients with previously untreated BRAF wild-type advanced melanoma, ORR was also higher with first-line nivolumab compared with chemotherapy (dacarbazine; 40 vs 13.9%) [3] . Median OS of patients treated with nivolumab was not reached [4] . The other approved anti-PD-1, pembrolizumab, has shown a similar benefit as nivolumab. The Phase I KEYNOTE 001 study showed a median OS of 20 months for all studied doses and was 28 months in ipilimumab-naive patients. Similar results were seen at 3 years [5] . The Phase II KEYNOTE 002 study showed the benefit of pembrolizumab compared with chemotherapy in patients previously treated with ipilimumab and a BRAF or MEK inhibitor, with an ORR of 22.2 and 27.6% for pembrolizumab 2 and 10 mg / kg, respectively, compared with 4.5% with chemotherapy. Median progression-free survival (PFS) at 2 years was significantly prolonged with pembrolizumab at both doses, but median OS was only significantly improved in patients treated with pembrolizumab 10 mg / kg (14.7 vs. 11 months with chemotherapy; p = 0.01; hazard ratio = 0.74) [6] . In the KEYNOTE 006 Phase III trial, first- or second-line pembrolizumab in BRAF mutant or wild-type melanoma patients had a higher response rate compared with ipilimumab. OS at 2 years with pembrolizumab was 55 versus 43% with ipilimumab [7] . At median follow-up of nearly 3 years, 33-month OS and PFS rates with pembrolizumab compared with ipilimumab were 50 versus 39% and 31 versus 14%, respectively [8] . Moreover, responses were durable in 104 patients who stopped pembrolizumab treatment after 2 years as per the study protocol; at a median follow-up of at 9.7 months after completing 2 years of","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"175-178"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36470687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COMBATING NRAS MUTANT MELANOMA: FROM BENCH TO BEDSIDE.","authors":"Ileabett M Echevarría-Vargas,&nbsp;Jessie Villanueva","doi":"10.2217/mmt-2017-0023","DOIUrl":"https://doi.org/10.2217/mmt-2017-0023","url":null,"abstract":"“ Oncogenic NRAS plays a critical role in melanoma initiation and maintenance; however, to date there are no effective ways to directly block the activity of mutant NRAS. ” NRAS is the second most common oncogenic driver in melanoma, mutated predominantly at codon 61 in almost 30% of all melanomas [1] . Tumors bearing NRAS mutations are highly aggressive and are associated with shorter patient survival [2] . Despite the prevalence of NRAS mutations and the severity of the resulting disease, treatment for NRAS mutant melanoma has lagged far behind BRAF-mutant tumors. Here, we summarize the status of the most promising strategies, highlighting the successes and the gaps that remain to be filled. GTP guanine-nucleotide exchange mutant form of to GAPs, leading to NRAS activation and persistent signaling that triggers and","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 4","pages":"183-186"},"PeriodicalIF":3.6,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36118032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitors in the treatment of advanced mucosal melanoma.","authors":"James C Kuo","doi":"10.2217/mmt-2017-0014","DOIUrl":"https://doi.org/10.2217/mmt-2017-0014","url":null,"abstract":"<p><p>Immunotherapy with immune checkpoint inhibitors is the standard of care in the treatment of advanced melanoma. Treatment outcome of these agents is less defined for the rare subtype of mucosal melanoma. In this single-institutional case series, the objective response rate was low at 11.8%, but durable response was seen, including a complete response to first-line ipilimumab and to second-line pembrolizumab. Survival remained poor; at the median follow-up of 10.1 months, the median progression-free survival and overall survival were 3.1 and 8.8 months respectively. Nevertheless, among the few responders, survival of up to 56+ months was observed. Other treatment strategies need to be explored to improve treatment outcome for this rare subtype.</p>","PeriodicalId":44562,"journal":{"name":"Melanoma Management","volume":"4 3","pages":"161-167"},"PeriodicalIF":3.6,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/mmt-2017-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36470685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}