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The Role of Anti-PD-1/PD-L1 in the Treatment of Skin Cancer

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Abstract

Skin cancers remain the most common group of cancers globally, and the incidence continues to rise. Although localized skin cancers tend to have excellent outcomes following surgical excisions, the less common cases that become surgically unresectable or metastatic have been associated with poor prognosis and suboptimal treatment responses to cytotoxic chemotherapy. Development of monoclonal antibodies to programmed cell death-1 receptor and its ligand (PD-1/PD-L1) have transformed the management of metastatic melanoma, squamous cell carcinoma, and Merkel cell carcinoma. These agents, as monotherapies, are associated with response rates of approximately 40–60%, many of which persist durably. Further efficacy is observed with combination immunotherapy in advanced melanoma. Early reports suggest similar activity in locally advanced or metastatic basal cell carcinoma. In this review, we describe common molecular features of skin cancers that may render them particularly susceptible to anti-PD-1/PD-L1 and detail results from key clinical trials of these agents across skin cancers. Overall, the superior response rates of skin cancer to anti-PD-1/PD-L1 compared with other solid tumor types are likely due, at least in part, to a high mutational burden and, in Merkel cell carcinoma, viral etiology. Although melanoma has been rigorously studied in the setting of anti-PD-1/PD-L1 treatment, more research is needed for the other skin cancer types to establish toxicity profiles, responses, and quality-of-life outcomes.

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Authors and Affiliations

  1. Vanderbilt University School of Medicine, 777 PRB, 2220 Pierce Ave, Nashville, TN, 37232, USA

    James Randall Patrinely Jr

  2. Department of Dermatology, Vanderbilt University Medical Center, Nashville, TN, USA

    Anna K. Dewan

  3. Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Douglas B. Johnson

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  1. James Randall Patrinely Jr
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  2. Anna K. Dewan
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  3. Douglas B. Johnson
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Correspondence to James Randall Patrinely Jr.

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Funding

This work was funded by a National Comprehensive Cancer Network (NCCN) Young Investigators Award (DBJ), an American Cancer Society institutional research Grant (DBJ), and the National Institutes of Health, Grant numbers: K23 CA204726 (DBJ), NIH R01CA227481 (DBJ).

Conflict of interest

Douglas B. Johnson serves on advisory boards for Array Biopharma, BMS, Incyte, Jansen, Merck, and Novartis; receives research funding from BMS and Incyte; and receives travel support from Genentech. J. Randall Patrinely Jr and Anna K. Dewan have no conflicts of interest that might be relevant to the contents of this manuscript.

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Patrinely, J.R., Dewan, A.K. & Johnson, D.B. The Role of Anti-PD-1/PD-L1 in the Treatment of Skin Cancer. BioDrugs 34, 495–503 (2020). https://doi.org/10.1007/s40259-020-00428-9

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