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Prognostic molecular testing in melanoma: ready for prime time? 黑色素瘤的预后分子检测:准备好了吗?
IF 3.6 Q1 Medicine Pub Date : 2017-12-01 Epub Date: 2017-07-31 DOI: 10.2217/mmt-2017-0013
Jennifer Keller, Laurence P Diggs, Eddy C Hsueh
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引用次数: 1
Anti-PD-1 and PD-L1 antibodies in metastatic melanoma. 转移性黑色素瘤中的抗pd -1和PD-L1抗体。
IF 3.6 Q1 Medicine Pub Date : 2017-12-01 Epub Date: 2017-11-21 DOI: 10.2217/mmt-2017-0018
Ester Simeone, Paolo A Ascierto
“ 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
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引用次数: 20
COMBATING NRAS MUTANT MELANOMA: FROM BENCH TO BEDSIDE. 对抗nras突变黑色素瘤:从实验室到床边。
IF 3.6 Q1 Medicine Pub Date : 2017-12-01 Epub Date: 2017-11-21 DOI: 10.2217/mmt-2017-0023
Ileabett M Echevarría-Vargas, Jessie Villanueva
“ 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
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引用次数: 7
Immune checkpoint inhibitors in the treatment of advanced mucosal melanoma. 免疫检查点抑制剂治疗晚期粘膜黑色素瘤。
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-10-04 DOI: 10.2217/mmt-2017-0014
James C Kuo

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.

免疫检查点抑制剂的免疫疗法是治疗晚期黑色素瘤的标准护理。对于罕见的粘膜黑色素瘤亚型,这些药物的治疗效果尚不明确。在这个单一机构的病例系列中,客观缓解率很低,为11.8%,但可以看到持久的缓解,包括对一线伊匹单抗和二线派姆单抗的完全缓解。生存率仍然很低;中位随访10.1个月时,中位无进展生存期和总生存期分别为3.1个月和8.8个月。然而,在少数应答者中,观察到的生存期长达56个月以上。需要探索其他治疗策略来改善这种罕见亚型的治疗效果。
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引用次数: 8
Anti-PD-1 monotherapy versus anti-PD1 plus anti-CTLA4 in advanced melanoma: how do we decide? 抗pd -1单药治疗与抗pd -1 +抗ctla4治疗晚期黑色素瘤:我们如何决定?
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-08-02 DOI: 10.2217/mmt-2017-0016
Lewis Au, Aine O'Reilly, James Larkin
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引用次数: 2
Advantages of whole-genome sequencing for identification of tumor etiology and clinically actionable genomic aberrations: lessons from the Australian Melanoma Genome Project. 全基因组测序鉴定肿瘤病因和临床可操作的基因组畸变的优势:来自澳大利亚黑色素瘤基因组计划的经验教训。
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-07-26 DOI: 10.2217/mmt-2017-0008
James S Wilmott, Nicholas K Hayward, Graham J Mann, Richard A Scolyer
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引用次数: 1
Can we improve melanoma detection methods? 我们能改进黑色素瘤的检测方法吗?
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-07-26 DOI: 10.2217/mmt-2017-0009
Riccardo Pampena, Caterina Longo
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引用次数: 1
Survivor and patient advocate: an interview with T.J. Sharpe. 幸存者和病人的倡导者:对T.J.夏普的采访。
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-07-31 DOI: 10.2217/mmt-2017-0012
Thomas J Sharpe

T.J. Sharpe speaks to Sebastian Dennis-Beron, Commissioning Editor: T.J. Sharpe is a stage IV melanoma patient who shares his journey through cancer in the Patient #1 Blog [1]. He was diagnosed in August 2012 with melanoma tumors in multiple organs; since then, he has undergone six surgeries and four immunotherapy treatments over two different clinical trials. The initial failures and subsequent significantly positive response have been chronicled in his blog posts since January 2013. His story is about life with a serious illness, and the mental and emotional hurdles a patient must clear. He writes how a cancer patient's challenges mirror those many face, and portrays life through the optimistic prism of a patient who is on the long, winding road toward overcoming melanoma's long odds and deadly consequences. He also shares the latest melanoma and oncology research breakthroughs and advocacy events, and initiatives to help others avoid, detect or educate themselves on cancer. As part of his advocacy, he attends cancer and melanoma conferences, reporting on the latest medical breakthroughs through his blog to other cancer patients. He also partners with advocacy organizations, clinical trial groups and the pharmaceutical industry to bring awareness to cancer research and developments. His efforts have been recognized by several organizations, including the Melanoma Research Foundation, Melanoma International Foundation, Patient Power, Forbes, Merck, GlaxoSmithKline, the Drug Information Association and the Milken Institute's FasterCures. In December 2014, he was able to share his story on Capitol Hill in a special session promoting immunotherapy research to lawmakers. A South Jersey native, T.J. lives in Fort Lauderdale with his wife Jennifer and two young children, Josie and Tommy. He is active in health and wellness initiatives, including melanoma/cancer awareness runs and bike rides, and an avid yoga participant. He also serves on the Board of Directors of A Prom to Remember, a 501

T.J.夏普采访了委托编辑塞巴斯蒂安·丹尼斯-伯龙:T.J.夏普是一名IV期黑色素瘤患者,他在患者1号博客上分享了他的癌症之旅[1]。2012年8月,他被诊断出患有多器官黑色素瘤;从那以后,他在两次不同的临床试验中接受了六次手术和四次免疫治疗。从2013年1月开始,他就在博客上记录了最初的失败和随后的积极回应。他的故事是关于患有严重疾病的生活,以及病人必须清除的精神和情感障碍。他写了一个癌症患者的挑战如何反映了许多人面临的挑战,并通过一个在漫长而曲折的道路上战胜黑色素瘤的病人的乐观的棱镜描绘了生活。他还分享了最新的黑色素瘤和肿瘤学研究突破和倡导活动,以及帮助他人避免、检测或自我教育癌症的举措。作为他倡导的一部分,他参加癌症和黑色素瘤会议,通过他的博客向其他癌症患者报告最新的医学突破。他还与倡导组织、临床试验团体和制药行业合作,提高人们对癌症研究和发展的认识。他的努力得到了几个组织的认可,包括黑色素瘤研究基金会、黑色素瘤国际基金会、患者力量、福布斯、默克、葛兰素史克、药物信息协会和米尔肯研究所的FasterCures。2014年12月,他在国会向议员们宣传免疫疗法研究的特别会议上分享了自己的故事。T.J.是南泽西人,他和妻子詹妮弗以及两个年幼的孩子乔西和汤米住在劳德代尔堡。他积极参与健康和保健活动,包括黑色素瘤/癌症宣传跑步和自行车骑行,也是一名狂热的瑜伽参与者。他也是A Prom to Remember(501)的董事会成员
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引用次数: 0
Utility of ipilimumab in melanoma patients who progress on anti-PD-1 therapy. ipilimumab在抗pd -1治疗进展的黑色素瘤患者中的应用
IF 3.6 Q1 Medicine Pub Date : 2017-09-01 Epub Date: 2017-07-26 DOI: 10.2217/mmt-2017-0010
Cesar E Ochoa, Richard W Joseph
survival
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引用次数: 8
Are PD-1 antibodies safe for use in metastatic uveal melanoma? PD-1抗体用于转移性葡萄膜黑色素瘤安全吗?
IF 3.6 Q1 Medicine Pub Date : 2017-05-01 Epub Date: 2017-05-10 DOI: 10.2217/mmt-2017-0007
Katy K Tsai, Alain P Algazi
prospective data support similar findings: 0 of 53 patients had objective response, 2-year OS rate was 7% and safety data showed 16 patients (30%) with grade 1–2 AEs and 19 patients (36%) with grade 3–4 AEs [25] . Grade 3–4 AEs were diarrhea, colitis and transaminitis. There was one possible treatment-related death in the setting of pancytopenia with subsequent cerebral hemorrhage and respiratory insufficiency. An abstract from a second Phase II study of ipilimumab 10 mg/kg (EudraCT 2010–024415–4) in 32 patients reported 15 patients (47%) with grade 3–4 AEs (abdominal pain, hypophysitis, emesis, diarrhea, asthenia, proctalgia, bone pain, urinary tract infection, hepatotoxicity, multi-organ failure, altered state of consciousness and vascular compression) [26] . Responses were similarly modest, with one partial response and six patients with stable disease at a median follow-up of 5.5 months.
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引用次数: 0
期刊
Melanoma Management
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