Kim Youjin, Lee Su Jin, Lee Ji Yun, Lee Se-Hoon, Sun Jong-Mu, Park Keunchil, An Ho Jung, Cho Jae Yong, Kang Eun Joo, Lee Ha-Young, Kim Jinsoo, Keam Bhumsuk, Kim Hye Ryun, Lee Kyoung Eun, Choi Moon Young, Lee Ki Hyeong, Ahn Myung-Ju
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
St Vincent's Hospital, Catholic University, Suwon, South Korea.
Cancer. 2017 Jun 1;123(11):1958-1964. doi: 10.1002/cncr.30537. Epub 2017 Jan 19.
Salivary gland cancers (SGCs) are uncommon and account for less than 5% of all head and neck cancers, but they are histologically heterogeneous. No specific therapy, including targeted agents, has consistently improved clinical outcomes in recurrent/metastatic SGC. Recent studies suggest that vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) play important roles in SGC. Nintedanib is a potent small-molecule, triple-receptor tyrosine kinase inhibitor (VEGFR1, VEGFR2, and VEGFR3; fibroblast growth factor receptor 1 [FGFR1], FGFR2, and FGFR3; and PDGFRα and PDGFRß). This study sought to determine the antitumor activity of nintedanib in patients with recurrent or metastatic SGC.
This open-label, multicenter, phase 2, single-arm study was conducted at 11 hospitals in South Korea. Patients with pathologically confirmed recurrent and/or metastatic SGC for whom at least 1 line of systemic chemotherapy had failed were enrolled. Nintedanib was given orally at 200 mg twice a day until disease progression or unacceptable toxicity. The primary endpoint was the response rate. The secondary endpoints were progression-free survival, overall survival, toxicity, and the disease-control rate. The Simon 2-stage minimax design was used.
The median age of the patients was 54 years, 60% were female, and 95% had an Eastern Cooperative Oncology Group performance status of 0 or 1. The majority of the patients had adenoid cystic carcinoma (65%), and 40% received at least 2 prior rounds of chemotherapy. After 20 patients were enrolled, the study was stopped because no responders were observed at stage I. There were no partial responses, but the disease-control rate was 75% (15 of 20). The median duration of stable disease was 8.2 months (range, 1.76-12.36 months). At the time of the data cutoff, with a median follow-up of 9.5 months, the median overall survival had not been reached, and the progression-free survival rate at 6 months was 60% (95% confidence interval, 0.34-0.79). Grade 3 adverse events included liver enzyme elevation (25%) and nausea/vomiting (5%). Four patients who required a dose reduction because of a grade 3 liver enzyme elevation showed no further grade 3 events.
Single-agent nintedanib did not yield a partial response but did achieve a 75% disease-control rate with long-term stabilization in SGC patients. Because of the high rate and long duration of disease control with a good safety profile, further investigation is warranted. Cancer 2017;123:1958-1964. © 2017 American Cancer Society.
涎腺癌（SGC）并不常见，占所有头颈癌的比例不到5%，但其组织学具有异质性。包括靶向药物在内，尚无特定疗法能持续改善复发/转移性SGC的临床结局。近期研究表明，血管内皮生长因子受体（VEGFR）和血小板衍生生长因子受体（PDGFR）在SGC中发挥重要作用。尼达尼布是一种强效小分子三受体酪氨酸激酶抑制剂（VEGFR1、VEGFR2和VEGFR3；成纤维细胞生长因子受体1 [FGFR1]、FGFR2和FGFR3；以及PDGFRα和PDGFRβ）。本研究旨在确定尼达尼布对复发或转移性SGC患者的抗肿瘤活性。
本开放标签、多中心、2期单臂研究在韩国的11家医院开展。纳入经病理证实为复发和/或转移性SGC且至少一线全身化疗失败的患者。尼达尼布口服给药，剂量为200 mg，每日两次，直至疾病进展或出现不可接受的毒性。主要终点为缓解率。次要终点为无进展生存期、总生存期、毒性和疾病控制率。采用西蒙2阶段最小最大设计。
患者的中位年龄为54岁，60%为女性，95%的东部肿瘤协作组体能状态为0或1。大多数患者患有腺样囊性癌（65%），40%的患者此前至少接受过2轮化疗。入组20例患者后，研究终止，因为在I期未观察到缓解者。无部分缓解，但疾病控制率为75%（20例中的15例）。疾病稳定的中位持续时间为8.2个月（范围为1.76 - 12.36个月）。在数据截止时，中位随访9.5个月，总生存期尚未达到，6个月时的无进展生存率为60%（95%置信区间，0.34 - 0.79）。3级不良事件包括肝酶升高（25%）和恶心/呕吐（5%）。4例因3级肝酶升高而需要减量的患者未再出现3级事件。
单药尼达尼布未产生部分缓解，但在SGC患者中疾病控制率达到75%，且能长期稳定病情。鉴于疾病控制率高、持续时间长且安全性良好，有必要进一步研究。《癌症》2017年；123:1958 - 1964。© 2017美国癌症协会
