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Metastatic Merkel Cell

Murtuza Bharmal, Alexia Marrel, Meliessa Hennessy, Fatoumata Fofana, Jérémy Lambert, Benoit Arnould
AIM: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC). METHODS: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel...
August 15, 2018: Journal of Comparative Effectiveness Research
Reinhard Dummer, Olivier Michielin, Mirjam Chantal Nägeli, Simone M Goldinger, Federico Campigotto, Ulrike Kriemler-Krahn, Herbert Schmid, Alberto Pedroncelli, Sara Micaletto, Dirk Schadendorf
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF -wild type (WT) and NRAS -WT metastatic melanoma. Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months...
2018: ESMO Open
Shailender Bhatia, Natalie J Miller, Hailing Lu, Natalie Vandeven Vandeven, Dafina Ibrani, Michi Shinohara, David Byrd, Upendra Parvathaneni, Rima M Kulikauskas, Jan Ter Meulen, Frank J Hsu, David M Koelle, Paul Nghiem
PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC). EXPERIMENTAL DESIGN: Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy...
August 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Mohammed T Lilo, Youdinghuan Chen, Robert E LeBlanc
Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas...
August 4, 2018: American Journal of Surgical Pathology
Daniela Femia, Natalie Prinzi, Andrea Anichini, Roberta Mortarini, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Andrea Maurichi, Ilaria Mattavelli, Massimo Milione, Nice Bedini, Ambra Corti, Maria Di Bartolomeo, Filippo de Braud, Sara Pusceddu
Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches...
August 2, 2018: Targeted Oncology
Justin P Bandino, Caitlin G Purvis, Blake R Shaffer, AbdAllah Gad, Dirk M Elston
BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy that shares cytologic, histopathologic, and immunohistochemical features with other small round blue cell (SRBC) tumors. Although the trabecular pattern is anecdotally associated with MCC, objective data are lacking. METHODS: This was a retrospective institutional review board-approved observational study conducted on microscopic images of 79 MCCs and 74 other SRBC tumors (desmoplastic small round cell tumor, primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, carcinoid, metastatic small cell lung cancer, non-Hodgkin small cell lymphoma, retinoblastoma, medulloblastoma, nephroblastoma, small cell osteosarcoma, and round cell liposarcoma)...
July 24, 2018: American Journal of Dermatopathology
Kashif Aziz, Amir Shahbaz, Muhammad Umair, Isaac Sachmechi
Avelumab is an anti-PD-L1 (programmed death-ligand 1) immune checkpoint inhibitor (ICIs) and the monoclonal antibody that constitutes a major development in the immunotherapy of cancer. In 2017, The European Medicine Agency (EMA) approved it as an orphan drug for treatment of gastric cancer. Avelumab has recently been approved in the United States, Europe and Japan for treatment of metastatic Merkel cell carcinoma (MCC). Avelumab inhibits the interaction of Programmed cell death protein 1 (PD-1) on immune cells with PD-L1 on tumor cells, thus banishing immunosuppressive signals and leading to enhanced immune cell activation...
2018: EXCLI Journal
Amanda Teets, Linda Pham, Emma Lan Tran, Lana Hochmuth, Rahul Deshmukh
Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma (UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite treatment with radiation therapy, surgery, and/or chemotherapeutic agents...
2018: Critical Reviews in Immunology
Kristina Buder-Bakhaya, Jessica C Hassel
Background: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma...
2018: Frontiers in Immunology
Timothy O'Brien, Derek G Power
Merkel-cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy arising most often in sun-exposed Caucasians who are immunosuppressed or the elderly. Patients with metastatic disease treated with chemotherapy have a median progression-free survival of just 3 months. This report describes a 58-year-old man with a background history of psoriasis treated with immunosuppressive therapy and subsequently diagnosed with metastatic MCC. Chemotherapy produced a partial response. Then, a novel immunotherapy agent, pembrolizumab, induced a complete response maintained for at least 19 months...
July 11, 2018: BMJ Case Reports
Steven K Jones, Kirk Douglas, Anthony F Shields, Olivia M Merkel
Using an orthotopic model of ovarian cancer, we studied the delivery of siRNA in nanoparticles of tri-block copolymers consisting of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) with and without a folic acid targeting ligand. A SKOV-3/LUC FRα overexpressing cell line was employed to mimic the clinical manifestations of ovarian cancer. Both targeted and non-targeted micelleplexes were able to effectively deliver siRNA to the primary tumor and its metastases, as measured by gamma scintillation counting and confocal microscopy...
September 2018: Biomaterials
U Wollina, G Hansel, J Schönlebe
Cutaneous polypoid melanoma is an uncommon subtype of malignant melanoma. The clinical behavior of this subtype has been described as aggressive. Tumors can be sessile or pedunculated. The typical patient is a younger adult. Authors have analyzed the case histories of patients with polypoid melanomas of the head and neck region treated at our clinic from 2001 to 2018. We identified 3 female patients with tumors of the neck and cheek. In contrast to other reports, all patients were older than 80-years of age...
May 2018: Georgian Medical News
Andrew Siref, Andrew Hendifar, Bonnie Balzer
A 63-year-old white man with no significant previous medical or surgical history presented with painless jaundice after 3 weeks of dark urine, yellow stools, and a 9-pound weight loss. Bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase were elevated, and a computed tomography scan detected a 10-cm, ill-defined mass at the porta hepatis compressing the common bile duct. He underwent endoscopic retrograde cholangiopancreatography with stenting and ultrasound-guided biopsies. Histologic sections showed a neoplastic population of small ovoid cells with a high N:C ratio, nuclear hyperchromasia, "smoky" chromatin and abundant mitotic figures, and characteristic of high-grade neuroendocrine carcinoma (HGNECA)...
July 6, 2018: American Journal of Dermatopathology
Kelly G Paulson, Shailender Bhatia
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer. The clinical impact of MCC has been increasing due to steadily rising incidence rates. Since 2001, more than 24,000 cases of MCC have been reported to the US National Program of Cancer Registries database, and in 2018, more than 2,500 incident cases are expected. MCC is highly aggressive, and one-third of patients will either present with or develop metastatic disease. Outcomes in patients with metastatic MCC have historically been poor; median time to progression with cytotoxic chemotherapy is only 3 months...
June 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Michael D Green, James A Hayman
The management of Merkel cell carcinoma (MCC) requires multidisciplinary care for optimal patient outcomes. Radiotherapy (RT) is most commonly used as adjuvant therapy to improve locoregional control in patients with MCC who undergo surgery. Additionally, it can sometimes be used as definitive monotherapy for patients who decline or are not candidates for surgery and as palliative treatment in those with metastatic MCC. This article discusses the indications, treatment considerations, and recommended dose prescriptions for RT in the management of early- and advanced-stage disease...
June 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Christopher K Bichakjian, Thomas Olencki, Sumaira Z Aasi, Murad Alam, James S Andersen, Rachel Blitzblau, Glen M Bowen, Carlo M Contreras, Gregory A Daniels, Roy Decker, Jeffrey M Farma, Kris Fisher, Brian Gastman, Karthik Ghosh, Roy C Grekin, Kenneth Grossman, Alan L Ho, Karl D Lewis, Manisha Loss, Daniel D Lydiatt, Jane Messina, Kishwer S Nehal, Paul Nghiem, Igor Puzanov, Chrysalyne D Schmults, Ashok R Shaha, Valencia Thomas, Yaohui G Xu, John A Zic, Karin G Hoffmann, Anita M Engh
This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence...
June 2018: Journal of the National Comprehensive Cancer Network: JNCCN
Melody J Xu, Susan Wu, Adil I Daud, Siegrid S Yu, Sue S Yom
BACKGROUND: Patients with metastatic Merkel cell carcinoma (mMCC) who experience disease progression on immunotherapy have limited additional standard options. Given evidence of synergism between radiation therapy (RT) and immunotherapy, two patients progressing on PD-1 inhibition were referred for short-course RT. CASE PRESENTATION: Two patients were found to have progressive mMCC on PD-1 inhibitor therapy and were treated with single-fraction palliative RT. Both patients were observed to have local control at irradiated regions, as well as durable abscopal response at unirradiated, out-of-field, sites of metastatic disease...
May 30, 2018: Journal for Immunotherapy of Cancer
Bruce A Feinberg, Murtuza Bharmal, Andrew J Klink, Chadi Nabhan, Hemant Phatak
AIM: Real-world evidence of charted treatment responses to cancer drug therapy was compared with medical record derived radiographic measurements of target lesions per Response Evaluation Criteria in Solid Tumors (RECIST). MATERIALS & METHODS: 15 physicians treating 59 metastatic Merkel cell cancer (mMCC) patients contributed patient-level data. A comparison of medical record reported best response with radiographic measurements per RECIST of pre- and post-treatment target lesions...
May 31, 2018: Future Oncology
Matt Shirley
Avelumab (Bavencio® ) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200...
June 2018: Targeted Oncology
Matthias M Weber, Christian Fottner
BACKGROUND: Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. METHOD: Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs...
2018: Oncology Research and Treatment
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