Apatinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck: A Single-Arm, Phase II Study

Background: Apatinib, a vascular endothelial growth factor receptor (VEGFR) blocker, has demonstrated encouraging antitumor activities and tolerable toxicities in various types of cancer. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) carries a poor prognosis, and treatment options are currently limited. The high VEGFR expression in R/MACCHN makes antiangiogenesis a potential effective treatment in patients with R/MACCHN. This study was conducted to explore the antitumor activity and safety of apatinib in patients with R/MACCHN. Methods: In this phase II single-arm, prospective study, patients aged 15-75 years with incurable R/MACCHN received apatinib at a dose of 500 mg once daily until intolerance or progression occurred. The primary endpoint was the 6-month progression-free survival (PFS) rate, which was based on RECIST version 1·1. The secondary endpoints included response rate, overall survival (OS) and safety. Efficacy was assessed in all dosed patients with at least one post-baseline tumor assessment. Findings: Among 68 patients treated with apatinib, 65 were evaluable for efficacy analysis, with a median follow-up time of 25·8 months. The 6-month, 12-month and 24-month PFS rates were 92·3% (95% confidence interval [CI]: 83–97·5%), 75·2% (95% CI: 61·5-84·0%) and 44·7% (95% CI: 32·3-57·5%), respectively. The objective response rate (ORR) and disease control rate (DCR), as assessed by investigators, were 46·2% (95% CI: 33·7–59·0%) and 98·5% (95% CI: 91·7–100·0%), respectively. The median duration of response was 17·7 months (interquartile range [IQR], 14·0-20·9). The 12-month and 24-month OS rates were 92·3% (95% CI: 83·0-97·5%) and 82·3% (95% CI: 70-90·4%), respectively. The most common adverse events of grades 3–4 were hypertension (5·9%), proteinuria (9·2%) and hemorrhage (5·9%). One patient developed a fatal hemorrhage. Interpretation: An encouraging PFS, a high ORR and a manageable safety profile were observed in this study. It seems that the administration of apatinib in R/MACCHN is likely to have a clinically meaningful therapeutic benefit and warrants further investigation. Trial Registration: Registered under http://www.clinicaltrials.gov (NCT02775370) Funding Statement: This work was supported by Shanghai Municipal Commission of Health and Family Planning (grant number 201640158)；the Clinical Research Program of 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine and the Shanghai Shenkang Hospital Development Center Refractory Diseases Project (project number 16CR2004A); Clinical Research Program of 9th People's Hospital, Shanghai Jiao Tong University School of Medicine (program number JYLJ201825). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This investigator-initiated phase II study was approved by the ethics committee of Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, and performed according to Good Clinical Practice Guidelines. All patients provided written informed consent before enrollment.