Anti‐programmed cell death‐1 therapy in nonmelanoma skin cancer

Winkler, Julia; Schneiderbauer, Roland; Bender, Carolin; Sedlaczek, Oliver; Fröhling, Stefan; Penzel, Roland; Enk, Alexander H.; Hassel, Jessica C.

doi:10.1111/bjd.14664

Cited by 78 publications

(60 citation statements)

References 17 publications

(34 reference statements)

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“…[42][43][44][45] Furthermore, murine studies and six independent case reports have shown responses to PD-1/PD-L1 inhibitors in unresectable cSCC ranging from disease stabilisation to complete response. [46][47][48][49] In conclusion, this is the largest HNcSCC tumor series to date to evaluate PD-L1 expression and the first to report an association with survival. PD-L1 expression is common in tumor cells and TILs and provides further evidence for a clinical trial of PD-1/PD-L1 inhibitors in…”

Section: Discussionmentioning

confidence: 77%

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

et al. 2017

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Programmed cell death (PD-1) and its ligand (PD-L1) inhibitors have shown clinical response in many tumours. PD-L1 data are limited in head and neck cutaneous squamous cell carcinoma (HNcSCC) and no clinical trials of PD-1/PD-L1 inhibitors are published. We performed PD-L1 immunohistochemistry on 74 cases of high risk HNcSCC with 38 matched metastases and evaluated clinicopathological associations, prognostic significance and heterogeneity in matched metastases. We observed PD-L1 expression in >5% of primary tumour cells in 29 cases (39.2%), primary tumour infiltrating lymphocytes (TILs) in 40 cases (70.2%), metastatic tumour cells in 15 cases (39.5%), and metastatic TILs in 18 cases (47.4%). PD-L1 expression in >5% of primary tumour cells was associated with an inflammatory phenotype (p = 0.04), and in primary TILs with clear margins (p = 0.05). PD-L1 expression in >5% of primary tumour cells (p = 0.01), primary TILs (p = 0.001), and metastatic TILs (p = 0.02) was associated with improved disease free survival. PD-L1 expression in >5% of tumour cells was heterogeneous between primary and metastatic tumours in 13 cases (34.2%). PD-L1 expression is common in HNcSCC supporting the rationale for a clinical trial of PD-1/ PD-L1 inhibitors. PD-L1 expression in tumour cells or TILs predicts longer disease free survival and demonstrates temperospatial heterogeneity. Disciplines Medicine and Health Sciences Publication DetailsRoper, E., Lum, T., Palme, C. E., Ashford, B., Ch'ng, S.

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Section: Discussionmentioning

confidence: 77%

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

et al. 2017

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“…Winkler et al [17] report on the case of a patient with metastatic basal cell carcinoma and response to pembrolizumab. Significant expression of PD-L1 on tumor and tumor-infiltrating immune cells was observed.…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma

et al. 2018

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Background: Metastatic basal cell carcinoma is rare and the prognosis is poor, with a lack of established treatment options for patients progressing on or after treatment with inhibitors of the hedgehog signaling pathway. Case Report: A man with pulmonary metastases of a basal cell carcinoma progressing after treatment with sonidegib and vismodegib was started on treatment with the anti-PD-1 antibody pembrolizumab. Upon treatment, rapid clinical improvement occurred, and after 5 cycles, the computed tomography scan showed near-complete remission of all tumor lesions. The tumor cells showed the absence of PD-L1 expression. Discussion: We report the first case of a patient with metastatic basal cell carcinoma experiencing an exceptional response to treatment with pembrolizumab in the absence of PD-L1 expression on the tumor cells. Immune checkpoint inhibition seems a promising treatment strategy for metastatic basal cell carcinoma. Our case suggests that the lack of PD-L1 expression does not rule out potential benefit from checkpoint inhibitor treatment.

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“…17 Recently, Winkler et al . 18 reported on a patient with metastatic basal cell carcinoma whose best response to treatment with pembrolizumab was stable disease for a few months. PD-L1 expression by IHC was found to be low in the patient’s pulmonary metastases.…”

Section: Discussionmentioning

confidence: 99%

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

et al. 2016

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Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA). The latter was performed using technology originally developed for the genome-wide detection of sub-chromosomal copy-number alterations (CNAs) in noninvasive prenatal testing and showed numerous CNAs including amplification of the 9p24.3-9p22.2 region containing PD-L1, PD-L2 and JAK2. Of interest, PD-L1, PD-L2 and JAK2 amplification is a characteristic of Hodgkin lymphoma, which is exquisitely sensitive to nivolumab. In conclusion, selected SMO antagonist-resistant metastatic basal cell carcinomas may respond to nivolumab based on underlying molecular genetic mechanisms that include PD-L1 amplification and high tumour mutational burden.

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Anti‐programmed cell death‐1 therapy in nonmelanoma skin cancer

Cited by 78 publications

References 17 publications

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma

Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma

Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy

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