Truong K, Peera M, Liu R, Wijaya M, Jones-Caballero M, Araujo R Ruiz, Fernandez-Penas P
Department of Dermatology, Westmead Hospital, Westmead, New South Wales, Australia.
Faculty of Medicine and Health, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia.
Australas J Dermatol. 2024 Dec;65(8):e248-e254. doi: 10.1111/ajd.14373. Epub 2024 Oct 25.
Basal cell carcinomas (BCCs) are the most common cancers worldwide. Although most BCCs are amenable to local treatment, there are limited therapeutic options for surgically unresectable locally advanced and metastatic BCCs. Activation of the sonic hedgehog signalling pathway plays a significant role in the development of most BCCs. Hedgehog pathway inhibitors (HPIs) can be used to inhibit this pathway. Efficacy and safety data on HPI use in Australia is scarce.
This study aims to present the effectiveness and safety of HPI at a tertiary dermatology referral centre.
We conducted a retrospective analysis of the clinical charts of all patients with BCC treated with an HPI at a tertiary Dermatology referral centre in New South Wales, Australia from 1 January 2016 to 1 July 2023.
Twenty-three patients with BCCs were treated with an HPI; 11 locally advanced, 8 multiple, 3 basal cell naevus syndrome and 1 metastatic. All patients were of Caucasian background, with a median age of 56. Across 41 treatment cycles, the median treatment duration was 4 months. The overall response rate (ORR) was 20/23 (87%) and complete response (CR) rate was 9/23 (39%); patients treated with sonidegib achieved an ORR of 11/12 (92%) and CR of 4/12 (33%), and vismodegib-treated patients achieved an ORR of 9/11 (82%) and CR of 5/11 (45%). Patients who responded to HPI treatment also responded to a subsequent HPI rechallenge. Common treatment emergent adverse events (TEAEs) included muscle spasms, dysgeusia and alopecia. Dysgeusia was more frequent with vismodegib than sonidegib (p = 0.0001). There was no evidence to suggest a difference in other TEAEs between the two HPIs. Four treatment cycles were stopped due to grade 3 muscle spasm.
In our cohort of 23 patients being treated with HPI, the ORR was 87% and CR was 39%. All patients who experienced TEAEs and had a drug holiday successfully responded to HPI rechallenge. TEAEs, particularly muscle spasms, are common reasons for treatment cessation. Clinicians should implement strategies to mitigate TEAE to improve drug survivability.
基底细胞癌（BCC）是全球最常见的癌症。尽管大多数基底细胞癌适合局部治疗，但对于手术无法切除的局部晚期和转移性基底细胞癌，治疗选择有限。音猬因子信号通路的激活在大多数基底细胞癌的发展中起重要作用。刺猬通路抑制剂（HPI）可用于抑制该通路。澳大利亚关于使用HPI的疗效和安全性数据很少。
本研究旨在介绍一家三级皮肤科转诊中心使用HPI的有效性和安全性。
我们对2016年1月1日至2023年7月1日在澳大利亚新南威尔士州一家三级皮肤科转诊中心接受HPI治疗的所有基底细胞癌患者的临床病历进行了回顾性分析。
23例基底细胞癌患者接受了HPI治疗；11例为局部晚期，8例为多发性，3例为基底细胞痣综合征，1例为转移性。所有患者均为白种人，中位年龄为56岁。在41个治疗周期中，中位治疗持续时间为4个月。总缓解率（ORR）为20/23（87%），完全缓解（CR）率为9/23（39%）；接受索尼德吉治疗的患者ORR为11/12（92%），CR为4/12（33%），接受维莫德吉治疗的患者ORR为9/11（82%），CR为5/11（45%）。对HPI治疗有反应的患者在后续再次使用HPI时也有反应。常见的治疗中出现的不良事件（TEAE）包括肌肉痉挛、味觉障碍和脱发。维莫德吉导致的味觉障碍比索尼德吉更常见（p = 0.0001）。没有证据表明两种HPI在其他TEAE方面存在差异。4个治疗周期因3级肌肉痉挛而停止。
在我们这组接受HPI治疗的23例患者中，ORR为87%，CR为39%。所有经历TEAE并停药的患者在再次使用HPI时均成功有反应。TEAE，尤其是肌肉痉挛，是治疗停止的常见原因。临床医生应采取策略减轻TEAE以提高药物耐受性。
