Phase II Study of the Safety and Antitumour Activity of Apatinib in Patients with Recurrent or Metastatic Adenoid Cystic Carcinoma of the Head and Neck

Abstract

Background: Apatinib has shown promising antitumour activities and tolerable toxicities in advanced gastric cancer and is being evaluated for many other cancers. Recurrent or metastatic adenoid cystic carcinoma of the head and neck (R/MACCHN) is linked to a poor prognosis and limited treatment options. This was a single-arm study (NCT02775370) conducted to determine prolonged progression-free survival (PFS) associated with apatinib administered in patients with R/MACCHN. Methods: In this phase II, single-arm trial, patients with R/MACCHN received apatinib 500 mg once daily until unacceptable toxicity, disease progression, or death. Patients with pathologically confirmed R/MACCHN who showed evidence of disease progression within 3 months or in whom at least one line of systemic chemotherapy failed were eligible. The primary end point was the 6-month PFS. The secondary end points included response rate, duration of response, overall survival (OS), and safety. Findings: Sixty-eight patients with R/MACCHN were evaluable (median follow-up, 13 months). The 6-month PFS rate was 87·9% (95% CI: 76·6%-99·1%), and the 12-month PFS rate was 50·7% (95% CI: 21·8%-79·7%) in the per-protocol population. The 12-month OS rate was 96·3% (95% CI: 91·3%-101·3%). Moreover, the best objective response rate and disease control rate were 46·2% (95% CI: 33·7-58·6%) and 98.5% (95% CI: 95·4-101·5), respectively. The median duration of response was 12·5 months (95% CI: 10·5-16·6 months). Common adverse events of grades 3-4 were hypertension (39·7%), hand-foot syndrome (27·9%), and proteinuria (19·1%). One patient developed a fatal haemorrhage of grade 5. Interpretation: Apatinib showed clinical activity with a manageable safety profile in patients with R/MACCHN. The findings suggested that apatinib is a meaningful therapeutic advance for this incurable disease. However, careful selection of patients is mandatory to minimise the risk of severe bleeding in future use. Clinical Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT02775370. Funding Statement: This work was supported by Shanghai Municipal Commission of Health and Family Planning (grant number 201640158) and Shanghai Shenkang Hospital Development Center Refractory Diseases Project (Project number 16CR2004A). 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 the guidelines of Good Clinical Practice Guidelines as defined by the International Conference on Harmonization and the Declaration of Helsinki. All patients gave written informed consent before enrollment.