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Case Reports
. 2024 Jun 27;16(1):173-180.
doi: 10.1159/000539592. eCollection 2024 Jan-Dec.

Hedgehog Pathway and Programmed Cell Death Protein-1 Inhibitors for Advanced Basal Cell Carcinoma

Babette J A Verkouteren  1   2 , An K L Reyners  3 , Maureen J B Aarts  2   4 , Klara Mosterd  1   2
Affiliations
Case Reports

Hedgehog Pathway and Programmed Cell Death Protein-1 Inhibitors for Advanced Basal Cell Carcinoma

Babette J A Verkouteren et al. Case Rep Dermatol. .

Abstract

Introduction: Basal cell carcinoma (BCC) is treated with local surgery or noninvasive treatment modalities. If a BCC remains untreated, it can develop into a locally advanced BCC or a metastatic BCC.

Case presentation: Here we report in detail the management of three complex advanced BCC (aBCC) after treatment failure with vismodegib. On all tumors, next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed; subsequently, patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anticancer drugs based on the molecular tumor profile. All patients showed partial response or stable disease following treatment with second line PD-1 inhibitors with an average duration of response of 12.3 months.

Discussion/conclusion: Immunotherapy can be a treatment option for aBCC resistant to hedgehog pathway inhibitor treatment. However, despite the high tumor mutational burden of aBCCs, immunotherapy does not always lead to a long response. Rechallenge or combining treatment of hedgehog inhibitors and PD-1 inhibitors by parallel or alternating cycles may be a strategy to lengthen the treatment response.

Keywords: Basal cell carcinoma; Checkpoint inhibitors; Hedgehog pathway inhibitor; Locally advanced basal cell carcinoma; Metastatic disease; Programmed cell death protein-1 inhibitors.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.
Fig. 1.
Clinical photograph of advanced basal cell carcinoma on the left abdomen before and during the complete treatment course (case 2). a aBCC on the left side of the abdomen at first presentation. b Axillary metastasis in the left axilla at first presentation. c aBCC on the abdomen after 4 months of vismodegib treatment. Clinically visible good response to vismodegib treatment. d aBCC on the abdomen after 6 months of vismodegib treatment. Several tumor nodules visible in the scar. e aBCC on the abdomen during treatment with pembrolizumab. Several tumor nodules are still visible. f aBCC on the abdomen after discontinuing pembrolizumab treatment. Clinically visible disease progression. g aBCC on the abdomen during the second cycle of vismodegib treatment. Disease progression is clinically visible.
See this image and copyright information in PMC

References

    1. Basset-Seguin N, Hauschild A, Grob JJ, Kunstfeld R, Dréno B, Mortier L, et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol. 2015;16(6):729–36. - PubMed
    1. Wysong A, Aasi SZ, Tang JY. Update on metastatic basal cell carcinoma: a summary of published cases from 1981 through 2011. JAMA Dermatol. 2013;149(5):615–6. - PubMed
    1. Stratigos AJ, Sekulic A, Peris K, Bechter O, Prey S, Kaatz M, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):848–57. - PubMed
    1. The drug Rediscovery protocol (DRUP trial). Available from: https://ClinicalTrials.gov/show/NCT02925234
    1. CPCT-02 biopsy protocol. Available from: https://ClinicalTrials.gov/show/NCT01855477

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