PD-L1 blockade with avelumab: A new paradigm for treating Merkel cell carcinoma

Barkdull, S.; Brownell, Isaac

doi:10.1080/15384047.2017.1394552

Cited by 17 publications

(16 citation statements)

References 11 publications

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“…However, to our knowledge, the prevalence of PD‐L1 expression in SmCC‐Cx has not been systematically studied. Merkel cell carcinoma (MCC), another virus‐related neuroendocrine malignancy, has significant rates of PD‐L1 expression and the US Food and Drug Administration (FDA) has recently granted accelerated approval for avelumab, an anti‐PD‐L1 monoclonal antibody, for the treatment of metastatic MCC …”

Section: Introductionmentioning

confidence: 99%

“…Merkel cell carcinoma (MCC), another virus-related neuroendocrine malignancy, has significant rates of PD-L1 expression and the US Food and Drug Administration (FDA) has recently granted accelerated approval for avelumab, an anti-PD-L1 monoclonal antibody, for the treatment of metastatic MCC. 22,23 With this background, we hypothesise that a subset of SmCC-Cx demonstrates expression of PD-L1.…”

Section: Introductionmentioning

confidence: 99%

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PD‐L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix

et al. 2019

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Aims Neuroendocrine carcinoma, small cell type, of the uterine cervix (SmCC‐Cx) is a rare human papilloma virus (HPV) related tumour with limited therapeutic options. Merkel cell carcinoma, another virus‐associated neuroendocrine malignancy, has significant programmed death ligand 1 (PD‐L1) expression rates. PD‐L1 expression has been reported in other malignancies of the cervix. We aimed to determine the prevalence of PD‐L1 in the context of mismatch repair protein (MMR) and RB1 expression status in SmCC‐Cx. Methods and results Ten cases of SmCC‐Cx were tested by immunohistochemistry for expression of PD‐L1, MLH1, MSH2, MSH6, PMS2, RB1, CD3, CD20 and for HPV by in‐situ hybridisation (ISH). PD‐L1 expression was scored quantitatively (H‐score) in tumour cells and lymphocytes (tumoral/peritumoral). PD‐L1 positivity was seen in seven cases, focal in most (H‐score range 3–140). Three of nine cases showed MMR deficiency. PD‐L1 expression levels correlated with MMR expression status: all three MLH1/PMS2‐deficient cases had a ≥5% PD‐L1 staining and an H‐score ≥10 (P = 0.01). RB1 was lost in four of nine cases, all PD‐L1 positive, but this correlation was not statistically significant. Seven of nine tumours were positive for HPV‐ISH; two of these had MLH1/PMS2 loss. Of the two HPV‐ISH negative tumours, one had MLS1/PMS2 loss. Conclusions PD‐L1 expression, predominantly focal, is seen in 70% of SmCC‐Cx, while loss of MMR expression is seen in 33% of SmCC‐Cx in our cohort. PD‐L1 expression in more than 10% of tumour cells is seen in a subset of tumours in association with loss of MMR expression. These patients may be amenable to immune checkpoint inhibitor therapy as a promising alternative for this aggressive disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PD‐L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix

et al. 2019

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“…This phenomenon has been highlighted in many different cancers and is one of the immune checkpoints targeted by immunotherapy. Recently, immunotherapy based on PD-1/PD-L1 inhibition [159][160][161] has been approved by the US FDA for patients with metastatic MCC. This therapy has already been used in other cancers for some years [162] and is also efficient in patients with metastatic MCC, although the response rate remains unsatisfactory [159,163].…”

Section: Immunotherapymentioning

confidence: 99%

Clinical Relevance of Liquid Biopsy in Melanoma and Merkel Cell Carcinoma

Boyer¹,

Cayrefourcq²,

Dereure

et al. 2020

Cancers

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Melanoma and Merkel cell carcinoma are two aggressive skin malignancies with high disease-related mortality and increasing incidence rates. Currently, invasive tumor tissue biopsy is the gold standard for their diagnosis, and no reliable easily accessible biomarker is available to monitor patients with melanoma or Merkel cell carcinoma during the disease course. In these last years, liquid biopsy has emerged as a candidate approach to overcome this limit and to identify biomarkers for early cancer diagnosis, prognosis, therapeutic response prediction, and patient follow-up. Liquid biopsy is a blood-based non-invasive procedure that allows the sequential analysis of circulating tumor cells, circulating cell-free and tumor DNA, and extracellular vesicles. These innovative biosources show similar features as the primary tumor from where they originated and represent an alternative to invasive solid tumor biopsy. In this review, the biology and technical challenges linked to the detection and analysis of the different circulating candidate biomarkers for melanoma and Merkel cell carcinoma are discussed as well as their clinical relevance.

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“…B. Tumorzellen [31]. Avelumab führte in 31,8 % der Patienten zu einem Therapieansprechen in den ersten 6 Monaten bei Chemotherapie-refraktären MCC-Patienten [32], wohingegen nur 6,7 % der Patienten mit metastasiertem MCC auf eine konventionelle Chemotherapie ansprachen [33]. Bei der Anwendung von Avelumab als Erstlinientherapie bei Patienten mit MCC im Stadium IV zeigte sich in einer Phase-II-Studie von DʼAngelo und Kollegen sogar eine Ansprechrate in den ersten 6 Monaten von 71,5 %, bei 28,6 % davon sogar ein vollständiges Ansprechen.…”

Section: Merkeunclassified