Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma

Zimmer, Lisa; Eigentler, Thomas; Kiecker, Felix; Simon, Jan C.; Utikal, Jochen; Mohr, Peter; Berking, Carola; Kämpgen, Eckhart; Dippel, Edgar; Stadler, Rudolf; Hauschild, Axel; Fluck, Michael; Terheyden, Patrick; Rompel, Rainer; Loquai, Carmen; Assi, Zeinab; Garbe, Claus; Schadendorf, Dirk

doi:10.1186/s12967-015-0716-5

Cited by 61 publications

(43 citation statements)

References 39 publications

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“…investigated the efficacy in everyday clinical practice. In this study, patients with previously treated mucosal melanoma showed a one‐year survival rate of roughly 14 %, while the percentage in those with previously treated unknown primary was 27 % . In another study by Zimmer et al., one‐year survival in patients with choroidal melanoma was 22 %, with a two‐year survival of 7 % .…”

Section: Clinical Efficacy Of Checkpoint Inhibitorssupporting

confidence: 44%

Immune checkpoint inhibitors: a milestone in the treatment of melanoma

Wilden

Lang

Mohr

et al. 2016

J Deutsche Derma Gesell

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SummaryIt has been known for decades that the immune system is able to detect and destroy tumor cells. In the past, this knowledge -mostly acquired through animal experiments -could not be used to benefit our patients, because immuno-oncological therapeutic approaches in humans had constantly failed over recent decades. With the exception of adjuvant interferon therapy, none of these approaches had found its way into everyday clinical practice, and only very few patients were able to enjoy long-term survival associated with good quality of life. With the advent of novel immunological approaches, the meaning of long-term survival as well as quality of life has been redefined for oncological patients. For the first time, a significant percentage of patients responds to treatment with immune checkpoint inhibitors, showing longterm remission and even cure. It has already become apparent that immunotherapy will in the future be one of the therapeutic mainstays in the treatment of metastatic melanoma as well as many other tumor types. The present review article presents the most important new treatment modalities, their mechanism of action, clinical data regarding treatment response, and adverse events to be expected.

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Section: Clinical Efficacy Of Checkpoint Inhibitorssupporting

confidence: 44%

Immune checkpoint inhibitors: a milestone in the treatment of melanoma

Wilden

Lang

Mohr

et al. 2016

J Deutsche Derma Gesell

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“…In an accompanying systematic review, the authors only identified three other papers reporting on patients with MUP who received immunotherapy (a phase II study, a retrospective cohort study, and one case report) and seven papers concerning targeted therapy (six case reports and one small prospective observational study reporting on one patient). The phase II single‐arm study reported a median OS duration of 9.9 months for patients with MUP who received ipilimumab . Other studies have reported on the survival in patients with stage III and IV MUP, but they have not specifically addressed treatment with novel agents …”

Section: Discussionmentioning

confidence: 99%

Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population‐based study

Verver

Veldt

Akkooi

et al. 2019

Intl Journal of Cancer

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Melanoma of unknown primary (MUP) may have a different biology to melanoma of known primary, but clinical trials of novel therapies (e.g., immune checkpoint or BRAF/MEK inhibitors) have not reported the outcomes in this population. We therefore evaluated the overall survival (OS) among patients with MUP in the era of novel therapy. Data for stage III or IV MUP were extracted from a nationwide database for the period 2003–2016, with classification based on the eighth edition of the American Joint Committee on Cancer criteria. The population was divided into pre‐ (2003–2010) and post‐ (2011–2016) novel therapy eras. Also, OS in the post‐novel era was compared between patients with stage IV MUP by whether they received novel therapy. In total, 2028 of 65,110 patients (3.1%) were diagnosed with MUP. Metastatic sites were known in 1919 of 2028 patients, and most had stage IV disease (53.8%). For patients with stage III MUP, the 5‐year OS rates were 48.5% and 50.2% in the pre‐ and post‐novel eras, respectively (p = 0.948). For those with stage IV MUP, the median OS durations were unchanged in the pre‐novel era and post‐novel era when novel therapy was not used (both 4 months); however, OS improved to 11 months when novel therapy was used in the post‐novel era (p < 0.001). In conclusion, more than half of the patients with MUP are diagnosed with stage IV and the introduction of novel therapy appears to have significantly improved the OS of these patients.

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“…Recently, targeted therapy has brought about encouraging results in the treatment of cutaneous melanoma; however, its implementation in OMM is lagging, owing in part to the lack of reliable genetic alterations reported in these tumors. Furthermore, some studies suggest that patients with mucosal melanomas do not benefit from the use of checkpoint inhibitors, as do patients with cutaneous melanoma . Thus, given the lack of treatment options for these rare tumors, improving the understanding of OMM tumorigenesis may prove useful for rational drug design.…”

Section: Introductionmentioning

confidence: 99%

Whole‐exome sequencing of oral mucosal melanoma reveals mutational profile and therapeutic targets

Lyu

Song

Chen

et al. 2018

The Journal of Pathology

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Oral mucosal melanoma (OMM) is a rare and aggressive subtype of melanoma with little known about its pathogenesis or carcinogenesis. We therefore performed whole-exome sequencing (WES) on 19 matched OMM tumor/normal pairs in order to gain insight into potential genetic drivers of tumor formation. For the first time, we describe the comprehensive mutational profile of OMM. Our data suggest that the genetic background of OMM differs from those of other melanoma subtypes. We identified recurrent mutations involving KIT, POLE, PTPRD, PTCHD2, and DMXL2. Notably, copy number analysis revealed recurrently amplified regions of 12q14 (57.9%, containing CDK4) and 5p15 (47.4%, containing TERT). CNV analysis in a separate cohort of 15 samples validated the frequent CNV in CDK4 and TERT. We also observed that the melanocyte development and pigmentation signaling pathway is frequently altered in OMM. Furthermore, our data suggest several altered genes that may be amenable for targeted therapy. We identified one patient with metastatic OMM in our cohort who was identified to harbor a targetable KIT mutation using our WES results. This patient was able to achieve complete remission following implementation of KIT-targeted therapy. These findings provide further insight into the genetic underpinnings of OMM development and suggest that patients with OMM may benefit from WES analysis to identify potential targetable genetic mutations. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Open-label, multicenter, single-arm phase II DeCOG-study of ipilimumab in pretreated patients with different subtypes of metastatic melanoma

Cited by 61 publications

References 39 publications

Immune checkpoint inhibitors: a milestone in the treatment of melanoma

Immune checkpoint inhibitors: a milestone in the treatment of melanoma

Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population‐based study

Whole‐exome sequencing of oral mucosal melanoma reveals mutational profile and therapeutic targets

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