García Ruiz Antonio J, García-Agua Soler Nuria, Herrera Acosta Enrique, Zalaudek Iris, Malvehy Josep
Pharmacology Department, University of Málaga, Institute of Biomedical Research in Malaga (IBIMA), Malaga, Spain.
Dermatology Department, Hospital Virgen de la Victoria, Malaga, Spain.
Drugs Context. 2022 Jul 7;11. doi: 10.7573/dic.2022-1-2. eCollection 2022.
Sonidegib and vismodegib are Hedgehog pathway inhibitors (HhIs) that play a relevant role in the management of locally advanced basal cell carcinoma (laBCC). This study compared the efficacy and safety of both HhIs based on their available data using effect size measures such as number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).
We reviewed data from pivotal trials of sonidegib (BOLT) and vismodegib (ERIVANCE). The NNT for sonidegib and vismodegib was calculated from objective response rate (ORR) values. The NNH was calculated from data relating to treatment discontinuation due to adverse events (AEs) and incidence of AEs. The LHH was calculated as the ratio between the corresponding NNH and NNT.
For sonidegib (200 mg), the NNT for ORR at 18 months was 1.65 (95% CI 1.35-2.01) whilst that for vismodegib (150 mg) at 21 months was 2.10 (95% CI 1.65-2.82). The NNH related to treatment discontinuation due to AEs was 1.9 (95% CI 1.6-2.5) for sonidegib and 1.8 (95% CI 1.4-2.2) for vismodegib. The LHH for sonidegib and vismodegib related to treatment discontinuation due to AEs was 1.14 and 0.84, respectively, whilst the LHH according to AEs of grade ≥3 was 1.41 for sonidegib and 0.85 for vismodegib.
Sonidegib showed a better benefit-risk ratio compared to vismodegib, being more likely to achieve therapeutic response than to AEs leading to discontinuation. These results should be confirmed in clinical practice and/or in a direct comparison study.
索尼德吉和维莫德吉是刺猬信号通路抑制剂（HhIs），在局部晚期基底细胞癌（laBCC）的治疗中发挥着重要作用。本研究基于可用数据，使用治疗所需人数（NNT）、伤害所需人数（NNH）以及受益或伤害可能性（LHH）等效应量指标，比较了两种HhIs的疗效和安全性。
我们回顾了索尼德吉（BOLT）和维莫德吉（ERIVANCE）关键试验的数据。索尼德吉和维莫德吉的NNT根据客观缓解率（ORR）值计算得出。NNH根据因不良事件（AE）导致的治疗中断数据和AE发生率计算得出。LHH计算为相应NNH与NNT的比值。
对于索尼德吉（200mg），18个月时ORR的NNT为1.65（95%CI 1.35 - 2.01），而对于维莫德吉（150mg），21个月时为2.10（95%CI 1.65 - 2.82）。因AE导致治疗中断的NNH，索尼德吉为1.9（95%CI 1.6 - 2.5），维莫德吉为1.8（95%CI 1.4 - 2.2）。因AE导致治疗中断的索尼德吉和维莫德吉的LHH分别为1.14和0.84，而≥3级AE的LHH，索尼德吉为1.41，维莫德吉为0.85。
与维莫德吉相比，索尼德吉显示出更好的效益风险比，更有可能实现治疗反应而非因AE导致治疗中断。这些结果应在临床实践和/或直接比较研究中得到证实。
