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.
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.
复制标题
DOI：
10.1111/jdv.14542
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Dummer R
中科院分区：
文献类型：
--
作者：
Lear JT;Migden MR;Lewis KD;Chang ALS;Guminski A;Gutzmer R;Dirix L;Combemale P;Stratigos A;Plummer R;Castro H;Yi T;Mone M;Zhou J;Trefzer U;Kaatz M;Loquai C;Kudchadkar R;Sellami D;Dummer R
局部晚期基底细胞癌（laBCC）或转移性基底细胞癌（mBCC）患者是两个难以治疗的人群，治疗选择有限。Sonidegib是一种刺猬通路抑制剂（HPI），基于BOLT试验的结果在laBCC中获得批准。在BOLT 18个月和30个月的分析中，评估sonidegib治疗laBCC和mBCC的长期疗效和安全性。BOLT （NCT01327053, ClinicalTrials.gov）是一项双盲ii期研究，从2011年7月至2013年1月纳入患者。符合条件的HPI‐treatment-naïve laBCC患者不能接受根治性手术/放疗或mBCC，随机分为sonidegib 200 mg （laBCC, n = 66; mBCC, n = 13）或800 mg （laBCC, n = 128; mBCC, n = 23）。根据中心和研究者回顾评估肿瘤反应。经过30个月的随访，在接受sonidegib 200mg（批准剂量）治疗的患者中，laBCC的客观缓解率为56.1%（中心）和71.2%（研究者），mBCC的客观缓解率为7.7%（中心）和23.1%（研究者）。肿瘤反应持续时间如下：laBCC的中位反应持续时间为26.1个月（中心）和15.7个月（研究者），mBCC的中位反应持续时间为24.0个月（中心）和18.1个月（研究者）。200毫克组5例laBCC患者和3例mBCC患者死亡。两组患者的中位总生存期均未达到；2年总生存率分别为93.2% （laBCC）和69.3% （mBCC）。在laBCC中，无论侵袭性或非侵袭性组织学，疗效相似。Sonidegib 200mg的安全性仍然优于800mg， 3/4级不良事件发生率（43.0%比64.0%）和导致停药的不良事件发生率（30.4%比40.0%）更低。Sonidegib在这些人群中继续显示出长期的有效性和安全性。这些数据支持每个局部治疗指南使用200毫克的sonidegib。
Patients with locally advanced basal cell carcinoma (laBCC) or metastatic BCC (mBCC), two difficult‐to‐treat populations, have had limited treatment options. Sonidegib, a hedgehog pathway inhibitor (HPI), was approved in laBCC based on results from the BOLT trial. To evaluate long‐term efficacy and safety of sonidegib in laBCC and mBCC in the BOLT 18‐ and 30‐month analyses. BOLT (NCT01327053, ClinicalTrials.gov), a double‐blind phase 2 study, enrolled patients from July 2011 until January 2013. Eligible HPI‐treatment–naïve patients with laBCC not amenable to curative surgery/radiotherapy or mBCC were randomized 1 : 2 to sonidegib 200 mg (laBCC, n = 66; mBCC, n = 13) or 800 mg (laBCC, n = 128; mBCC, n = 23). Tumour response was assessed per central and investigator review. With 30 months of follow‐up, among patients treated with sonidegib 200 mg (approved dose), objective response rates were 56.1% (central) and 71.2% (investigator) in laBCC and 7.7% (central) and 23.1% (investigator) in mBCC. Tumour responses were durable as follows: median duration of response was 26.1 months (central) and 15.7 months (investigator) in laBCC and 24.0 months (central) and 18.1 months (investigator) in mBCC. Five patients with laBCC and three with mBCC in the 200‐mg arm died. Median overall survival was not reached in either population; 2‐year overall survival rates were 93.2% (laBCC) and 69.3% (mBCC). In laBCC, efficacy was similar regardless of aggressive or non‐aggressive histology. Sonidegib 200 mg continued to have a better safety profile than 800 mg, with lower rates of grade 3/4 adverse events (43.0% vs. 64.0%) and adverse events leading to discontinuation (30.4% vs. 40.0%). Sonidegib continued to demonstrate long‐term efficacy and safety in these populations. These data support the use of sonidegib 200 mg per local treatment guidelines.
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
13.8
作者：
Ally, Mina Sarah;Aasi, Sumaira;Tang, Jean Yuh
通讯作者：
Tang, Jean Yuh
影响因子：
10.3
作者：
Danial, C.;Lingala, B.;Chang, A. L. S.
通讯作者：
Chang, A. L. S.
DOI：
10.1158/1078-0432.ccr-12-3654
发表时间：
2013-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jimeno A;Weiss GJ;Miller WH Jr;Gettinger S;Eigl BJ;Chang AL;Dunbar J;Devens S;Faia K;Skliris G;Kutok J;Lewis KD;Tibes R;Sharfman WH;Ross RW;Rudin CM
通讯作者：
Rudin CM
影响因子：
4.2
作者：
Pan, Shifeng;Wu, Xu;Dorsch, Marion
通讯作者：
Dorsch, Marion