Defining and recognising locally advanced basal cell carcinoma

Amici, J.-M.; Battistella, Maxime; Beylot‐Barry, M.; Chatellier, Anne; Dalac-Ra, Sophie; Dréno, Brigitte; Falandry, Claire; Froget, Nicolas; Giacchero, Damien; Grob, Jean-Jacques; Guerreschir, Pierre; Leccia, Marie‐Thérèse; Malard, O.; Mortier, Laurent; Routier, Émilie; Stefan, A.; Stefan, Dinu; Stoebner, Pierre‐Emmanuel; Basset-Séguin, Nicole

doi:10.1684/ejd.2015.2641

Cited by 26 publications

(13 citation statements)

References 15 publications

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“…For nonadvanced BCC, primary treatment options include surgical excision, Mohs micrographic surgery, cryotherapy and radiation therapy . In a subset of cases, BCCs can become excessively invasive or destructive; these are known as advanced BCCs and are defined as BCCs in which current treatment modalities are contraindicated, potentially because of clinical or patient‐driven factors . Complex cases of BCC include locally advanced BCC (laBCC)—in which significant tissue invasion of the tumour can result in considerable deformity and surgical excision is unacceptable—and metastatic BCC (mBCC), whose prognosis is poor, with high morbidity and mortality .…”

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confidence: 99%

Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study

et al. 2019

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Background Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. Objectives This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. Methods Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent. The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety end points included adverse event monitoring and reporting. Results The study enrolled 230 patients, 79 and 151 in the 200-mg and 800-mg groups, respectively, of whom 8% and 3.3% remained on treatment by the 42month cutoff, respectively. The ORRs by central review were 56% [95% confidence interval (CI) 43-68] for laBCC and 8% (95% CI 0Á2-36) for mBCC in the 200-mg group and 46Á1% (95% CI 37Á2-55Á1) for laBCC and 17% (95% CI 5-39) for mBCC in the 800-mg group. No new safety concerns emerged. Final 42-month efficacy and safety results from the BOLT study, R. Dummer et al. 1373Fig 3. Objective response rates by central review across all BOLT (Basal Cell Carcinoma Outcomes with LDE225 Treatment) analyses in patients receiving sonidegib 200 mg daily. 17,19,20 Results are for the intent-to-treat population. BCC, basal cell carcinoma; laBCC, locally advanced BCC; mBCC, metastatic BCC; ORR, objective response rate. Fig 4. Kaplan-Meier plots of duration of response per central review in patients receiving sonidegib 200 mg daily (responders only). BCC, basal cell carcinoma; laBCC, locally advanced BCC; mBCC, metastatic BCC; mo, months. 1374 Final 42-month efficacy and safety results from the BOLT study, R. Dummer et al. The data are presented as n (%). Results are for the safety population. AE, adverse event; BOLT, Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment; SAE, serious AE. Final 42-month efficacy and safety results from the BOLT study, R. Dummer et al. 1375 Fig 6. Adverse events in ≥ 20% of patients treated with sonidegib 200 mg and 800 mg daily CK, creatine kinase.

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Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study

et al. 2019

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“…Their definition includes tumor factors, operability factors, and patient factors. 6 In sum, these different groups define laBCCs as large, aggressive, or recurrent tumors that are deeply invasive and require extensive surgery. Treating laBCCs requires a multi-disciplinary approach where different treatment modalities including surgery, radiation therapy, Hedgehog Pathway Inhibitors (HHI), and immunotherapy, can be considered.…”

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confidence: 99%

Current Perspectives in the Treatment of Locally Advanced Basal Cell Carcinoma

Gupta¹,

ES²

2022

DDDT

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Basal cell carcinoma (BCC) is the most common cancer in Caucasians, and its incidence continues to rise. Generally, BCCs have good outcomes when diagnosed and treated early. However, 1–10% of patients will develop advanced disease due to either delays in accessing treatment or aggressive tumors that may be refractory to treatment. Locally advanced basal cell carcinomas (laBCCs) are large, aggressive, or recurrent tumors that have the potential to invade surrounding tissues including bone, cartilage, nerve, and muscle. Treatment requires a multi-disciplinary approach where different modalities including surgery, radiation therapy, Hedgehog Pathway Inhibitors, and immunotherapy can be considered.

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“…Standard excision or curettage and electrodessication are often used for low-risk lesions, and Mohs micrographic surgery is often effective for treating high-risk tumors [ 4 ]. However, a subset of advanced BCC cases that includes both locally advanced BCC (laBCC) and metastatic BCC (mBCC) are not amenable to surgery due to high morbidity and risk for severe disfigurement [ 1 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

Doan

Chen²,

Nawas

et al. 2021

Oncotarget

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Although basal cell carcinoma (BCC) is often managed successfully with surgery, patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who are not candidates for surgery or radiotherapy have limited treatment options. Most BCCs result from aberrant Hedgehog pathway activation in keratinocyte tumor cells, caused by sporadic or inherited mutations. Mutations in the patched homologue 1 gene that remove its inhibitory regulation of Smoothened homologue (SMO) or mutations in SMO that make it constitutively active, lead to Hedgehog pathway dysregulation and downstream activation of GLI1/2 transcription factors, promoting cell differentiation and proliferation. Hedgehog inhibitors (HHIs) block overactive signaling of this pathway by inhibiting SMO and are currently the only approved treatments for advanced BCC. Two small-molecule SMO inhibitors, vismodegib and sonidegib, have shown efficacy and safety in clinical trials of advanced BCC patients. Although these agents are effective and tolerable for many patients, HHI resistance occurs in some patients. Mechanisms of resistance include mutations in SMO, noncanonical cell identity switching leading to tumor cell resistance, and non-canonical pathway crosstalk causing Hedgehog pathway activation. Approaches to managing HHI resistance include switching HHIs, HHI and radiotherapy combination therapy, photodynamic therapy, and targeting Hedgehog pathway downstream effectors. Increasing understanding of the control of downstream effectors has identified new therapy targets and potential agents for evaluation in BCC. Identification of biomarkers of resistance or response is needed to optimize HHI use in patients with advanced BCC. This review examines HHI resistance, its underlying mechanisms, and methods of management for patients with advanced BCC.

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Defining and recognising locally advanced basal cell carcinoma

Cited by 26 publications

References 15 publications

Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study

Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study

Current Perspectives in the Treatment of Locally Advanced Basal Cell Carcinoma

Switching Hedgehog inhibitors and other strategies to address resistance when treating advanced basal cell carcinoma

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