Long‐term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30‐month analysis of the randomized phase 2 BOLT study

Lear, John T.; Migden, Michael R.; Lewis, Karl D.; Chang, Anne Lynn S.; Guminski, Alexander; Gutzmer, Ralf; Dirix, L.; Combemale, P.; Stratigos, Alexander J.; Plummer, Ruth; Castro, Henry; Yi, Tingting; Mone, Manisha; Zhou, Jocelyn; Trefzer, Uwe; Kaatz, Martin; Loquai, Carmen; Kudchadkar, Ragini R.; Sellami, Dalila; Dummer, Reinhard

doi:10.1111/jdv.14542

Cited by 166 publications

(210 citation statements)

References 31 publications

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“…Additionally, disease control rate remained unchanged between 30 and 12 months at a value of 92.3% for the 200 mg arm and 91.3% for the 800 mg arm per central review. Per central review at 30 months, the estimated median DOR for the 200 mg arm was 24.0 months; for the 800 mg arm, the Data taken from [14][15][16].…”

Section: -Month Follow-upmentioning

confidence: 99%

Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Chen¹,

Aria²,

Silapunt³

et al. 2017

Future Oncol.

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Sonidegib, a hedgehog pathway inhibitor, was approved by the US FDA for the treatment of locally advanced basal cell carcinoma which cannot be readily treated with surgery or radiotherapy. The pharmacology and pharmacokinetics of sonidegib will be discussed in this review. Additionally, an in-depth analysis of the BOLT trial and data from the 30-month update will be included. This will serve as an update to a previously published article which reported the 12-month update of the BOLT trial. BackgroundBasal cell carcinoma (BCC) is the most common skin cancer in humans. Annually, there are 2.8 million cases that result in approximately 3000 deaths [1]. The use of surgical excision for the treatment of BCC results in a 5-year cure rate close to 90% [2,3]. The 5-year recurrence rate decreases to 0.7-2.4% when Mohs micrographic surgery (MMS) is performed [4][5][6][7]. Alternative nonsurgical approaches include cryotherapy, electrodesiccation and curettage, photodynamic therapy, radiation, or topical agents such as imiquimod or 5-fluorouracil. These options usually confer a lower cure rate and lack confirmation of tumor clearance on histology. Although metastasis of BCC has a very low incidence of 0.0028-0.

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Section: -Month Follow-upmentioning

confidence: 99%

Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Chen¹,

Aria²,

Silapunt³

et al. 2017

Future Oncol.

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show abstract

“…It should be noted that no cases of rhabdomyolysis (defined as creatine kinase elevations >10-fold higher than the pretreatment or baseline level [or >10 times the upper limit of the normal range if no baseline level was reported] in conjunction with a 1.5-fold increase from baseline in serum creatinine) were confirmed by an independent safety review committee composed of experts on muscle toxicity [23]. With 30 months of data, sonidegib showed a similar AE profile to that seen at 18 months [11,23].…”

Section: Sonidegib: Qol Data From the Bolt Trialmentioning

confidence: 86%

“…In the ERIVANCE trial at 30 months, patients with laBCC or mBCC showed investigator-assessed objective response rates of 60.3% and 48.5%, respectively [10]. In the BOLT study, patients treated with sonidegib at 30 months showed objective response rates of 71.2% for laBCC and 23.1% for mBCC (per investigator review) [11]. Because advanced BCC is associated with sun exposure, it occurs often on visible parts of the body, such as the face, ears, and neck [12].…”

Section: Introductionmentioning

confidence: 99%

Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

Migden¹

2017

J Clin Exp Dermatol Res

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Basal cell carcinoma (BCC), the most common form of cancer, affects approximately 2 million people annually in the US. Aberrant activation of the hedgehog signaling pathway plays an important role in BCC. Two inhibitors of the SMO component of hedgehog signaling, vismodegib and sonidegib, are currently approved for use in advanced BCC, including locally advanced BCC (laBCC) and metastatic BCC (mBCC), depending on the country of approval. Location of lesions and fears about changes in appearance may affect the quality of life (QoL) of patients with advanced BCC. In addition, QoL itself is an outcome for advanced BCC. The key clinical trials for vismodegib (ERIVANCE and STEVIE) and for sonidegib (BOLT) included QoL as secondary end points, using different questionnaires for assessment. In ERIVANCE, Short Form-36 for assessing QoL showed no changes from baseline on either the physical or emotional domains. In STEVIE, the Skindex-16 for assessing QoL showed that treatment with vismodegib was associated with clinically meaningful improvement in the emotional domain. To determine QoL, BOLT used predetermined subscales related to skin specifically from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC H&N35. Both the QLQ-C30 and H&N35 selected subscales showed either maintenance or improvement from baseline. Factors affecting QoL during treatment of patients with advanced BCC include baseline QoL, having fewer comorbidites, and having better initial mental health status. In addition, patients whose lesions were advanced, but were not as large as others or not located in visible areas (ie, head and neck) reported better QoL. Treatment-emergent adverse events (AEs) have an impact on QoL in patients with advanced BCC. Most of the AEs reported in trials for vismodegib and sonidegib were grade 1-2. Using techniques to manage AEs effectively may help improve QoL for those whose QoL decreases during treatment.

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“…HPIs offer a therapeutic option of considerable efficacy for patients with difficult‐to‐treat inoperable or recurrent locally advanced and metastatic basal cell carcinoma by inhibiting SMO of the Hh pathway and the downstream inhibition of the transcription of target genes implicated in BCC development and differentiation . Investigator‐assessed response rates were 60.3% for laBCC and 48.5% for mBCC with vismodegib and 71.2% for laBCC with sonidegib . Given the rarity of mBCC (<0.1%) 1 , there are only limited reports of chemotherapy for patients with mBCC with transient or disappointing results or intolerable toxicity .…”

Section: Meeting the Needs Of Advanced Bcc: Treatment With Hedgehog Imentioning

confidence: 99%

“…Given the rarity of mBCC (<0.1%) 1 , there are only limited reports of chemotherapy for patients with mBCC with transient or disappointing results or intolerable toxicity . For mBCC, the median progression‐free survival (PFS), with vismodegib at approved dosing, was 9.3 months in the ERIVANCE study and 13.1 months in the STEVIE study , and with sonidegib was 13.1 months in the BOLT study . As HPIs become increasingly incorporated in the clinical practice, dermatologists will face many challenges during the monitoring of treatment of patients with HPI: to optimally schedule clinical follow‐up, to assess efficacy and tumor responses, to monitor for toxicity and tolerability issues, and to inform patients about which adverse events to expect and how to effectively cope.…”

Section: Meeting the Needs Of Advanced Bcc: Treatment With Hedgehog Imentioning

confidence: 99%

A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors

et al. 2019

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The Hedgehog pathway inhibitors (HPIs), vismodegib and sonidegib, are increasingly employed in the treatment of patients with advanced basal cell carcinoma (BCC). The aim of this review is to create a synthesis of available information in the literature regarding the follow‐up of patients with advanced BCC treated with HPIs and to provide the treating physician with a structured practical guide to standardize clinical practice. Several challenges during treatment are addressed: to optimally evaluate tumor responses, to differentiate between resistance (HPI rechallenge not possible) and recurrence (HPI rechallenge may be possible) in case of BCC regrowth, to readily assess for toxicity and tolerability issues, to provide patients with practical ways and behaviors to effectively cope with adverse events, and to improve patient adherence and quality of life. Implications for Practice This is a practical guide for clinical practice regarding the monitoring and follow‐up of patients with advanced basal cell carcinoma (BCC) during treatment with the Hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib. This review aims to bridge the gap in knowledge of assessing tumor response for BCC with both an externally visible component and an infiltrating component measurable with imaging. Furthermore, it addresses the follow‐up for adverse events as a challenging multistep process involving practices aiming to readily assess new‐onset symptoms of HPI toxicity, perform total‐body skin examination, and improve patient adherence and quality of life.

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Long‐term efficacy and safety of sonidegib in patients with locally advanced and metastatic basal cell carcinoma: 30‐month analysis of the randomized phase 2 BOLT study

Cited by 166 publications

References 31 publications

Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Treatment of Advanced Basal Cell Carcinoma with Sonidegib: Perspective from the 30-Month Update of the BOLT Trial

Quality of Life for Patients with Advanced Basal Cell Carcinoma Treated with Hedgehog Signaling Pathway Inhibitors

A Practical Guide for the Follow-Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors

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