Dataset Information

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

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.

SUBMITTER: Verkouteren BJA

PROVIDER: S-EPMC11250645 | biostudies-literature | 2024 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

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

Verkouteren Babette J A BJA Reyners An K L AKL Aarts Maureen J B MJB Mosterd Klara K

Case reports in dermatology 20240101 1

<h4>Introduction</h4>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.<h4>Case presentation</h4>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 ...[more]

PMID: 39015399

Similar Datasets

Project description:Abnormal activation of hedgehog pathway signaling is a key driver in the pathogenesis of basal cell carcinoma (BCC). Vismodegib, a first-in-class small-molecule inhibitor of hedgehog pathway signaling, is approved by regulatory authorities for the treatment of adults who have metastatic BCC or locally advanced BCC that has recurred after surgery, or who are not candidates for surgery and who are not candidates for radiation. A second inhibitor, sonidegib, was also recently approved for the same patient group with locally advanced BCC. Adverse events (AEs) commonly observed in hedgehog pathway inhibitor (HPI)-treated patients include muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and asthenia (fatigue). These AEs are thought to be mechanistically related to inhibition of the hedgehog pathway in normal tissue. Although the severity of the majority of AEs associated with HPIs is grade 1-2, the long-term nature of these AEs can lead to decreased quality of life, treatment interruption, and in some cases discontinuation, all of which might affect clinical outcome. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to HPIs in advanced BCC are described. These observations represent the first step toward the development of mechanism-based preventive and management strategies. Knowledge of these AEs will allow health care professionals to provide appropriate counseling and supportive care interventions, all of which will contribute to improved quality of life and optimal benefit from therapy.Implications for practiceThe hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib represent a therapeutic breakthrough for patients with advanced basal cell carcinoma. However, the nature of the low-grade adverse events (AEs) commonly observed in HPI-treated patients, including muscle spasms, ageusia/dysgeusia, alopecia, weight loss, and fatigue, can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described, with the goal of enabling health care professionals to provide appropriate counseling and supportive care interventions to their patients.

Dataset Information

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

Introduction

Case presentation

Discussion/conclusion

Publications

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

Similar Datasets

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