替匹法尼治疗复发性、转移性 HRAS 突变型唾液腺癌。
Tipifarnib in recurrent, metastatic HRAS-mutant salivary gland cancer.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Division of Neuroradiology, Brigham & Women's Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts.
出版信息
Cancer. 2020 Sep 1;126(17):3972-3981. doi: 10.1002/cncr.33036. Epub 2020 Jun 18.
BACKGROUND
To the authors' knowledge, there are no approved therapies for recurrent, metastatic (R/M) salivary gland carcinoma (SGC), but molecularly targeted therapies warrant ongoing investigation. In the current study, the authors have reported on the efficacy of tipifarnib in patients with aggressive HRAS-mutant, R/M SGC.
METHODS
The current prospective, nonrandomized, multicenter, international cohort study involved 8 centers and was conducted from May 2015 to June 2019. The median follow-up was 22 months (range, 6-55 months). Subjects with HRAS-mutant R/M SGC (any histology) and disease progression within the last 6 months were enrolled. Tipifarnib was dosed orally twice daily. The authors determined the objective response rate using Response Evaluation Criteria in Solid Tumors (version 1.1), duration of response, and molecular predictors of response.
RESULTS
A total of 13 patients with R/M SGC were enrolled; all had received prior systemic therapy (1-3 regimens). One objective response was observed; an additional 7 of 12 evaluable patients (58%) had stable disease as their best response with a median duration of 9 months (range, 3-14 months). Five of 7 patients had >10% tumor regression and 6 of 7 had stable disease lasting >6 months. Q61R was the most frequent activating HRAS mutation noted (7 of 13 patients; 54%), but gene variant and allele frequency did not correlate with outcomes. The median progression-free survival was 7 months (95% confidence interval, 5.9-10.1 months), and the median overall survival was 18 months (95% confidence interval, 9.6-22.4 months) with approximately 58.6% of patients alive at 1 year. Survival was similar regardless of HRAS mutant variant or co-occurring PIK3CA alterations. No participant discontinued treatment because of toxicity.
CONCLUSIONS
Tipifarnib resulted in modest clinical activity with a promising disease control rate among patients with HRAS-mutant, R/M SGC who developed disease progression within the last 6 months.
背景
据作者所知，目前尚无针对复发性、转移性（R/M）唾液腺癌（SGC）的批准疗法，但分子靶向治疗仍值得进一步研究。在本研究中，作者报告了替皮法尼在具有侵袭性 HRAS 突变、R/M SGC 的患者中的疗效。
方法
本前瞻性、非随机、多中心、国际队列研究共涉及 8 个中心，于 2015 年 5 月至 2019 年 6 月进行。中位随访时间为 22 个月（范围 6-55 个月）。招募了 HRAS 突变 R/M SGC（任何组织学）且在过去 6 个月内疾病进展的患者。替皮法尼每日口服两次。作者使用实体瘤反应评价标准（第 1.1 版）确定客观缓解率、缓解持续时间和反应的分子预测因子。
结果
共纳入 13 例 R/M SGC 患者；所有患者均接受过系统治疗（1-3 种方案）。观察到 1 例客观缓解；12 例可评估患者中另外 7 例（58%）的最佳反应为疾病稳定，中位缓解持续时间为 9 个月（范围 3-14 个月）。7 例患者中有 5 例肿瘤消退>10%，7 例患者中有 6 例疾病稳定持续>6 个月。Q61R 是最常见的激活 HRAS 突变（13 例患者中有 7 例；54%），但基因变异和等位基因频率与结局无关。中位无进展生存期为 7 个月（95%置信区间，5.9-10.1 个月），中位总生存期为 18 个月（95%置信区间，9.6-22.4 个月），约有 58.6%的患者在 1 年内存活。生存情况与 HRAS 突变变异或同时存在的 PIK3CA 改变无关。没有患者因毒性而停止治疗。
结论
替皮法尼在最近 6 个月内疾病进展的 HRAS 突变、R/M SGC 患者中具有一定的临床活性，疾病控制率有希望。
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