Efficacy and Safety of Surufatinib for Recurrent or Metastatic Malignant Salivary Gland Tumors: An Open-Label, Single-Arm, Phase II Study.

Recurrent or metastatic malignant salivary gland tumors (R/M MSGTs) of the head and neck portend a poor prognosis, and therapeutic options are currently limited. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI) that selectively targets VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent studies have demonstrated encouraging efficacy of small molecule antiangiogenic inhibitors in head and neck cancer. This study was therefore conducted to investigate the antitumor activity and safety of surufatinib in R/M MSGT patients. Patients aged 18-75 years with incurable and progressive R/M MSGTs received surufatinib at a dose of 300 mg once daily until intolerance or disease progression occurred. Based on a Simon's two-stage minimax design, 13 patients would be enrolled in stage 1; if 1 or more responses were observed, the trial would proceed to stage 2 in which an additional 14 patients would be enrolled, for a total sample size of 32 patients. The primary endpoint was objective response rate (ORR) as assessed by RECIST 1.1 criteria, and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. This study was prospectively registered with ClinicalTrials.gov (NCT04910854). From May 2019 to March 2023, 12 patients were enrolled and received at least one dose of treatment. The median age was 45.5 years (range 27-60), 83.3% were female, and 41.7% had an ECOG performance status of 2. The most common histological tumor types were adenoid cystic carcinoma (ACC, 41.7%) and mucoepidermoid carcinoma (MEC, 41.7%). The most frequent metastatic sites were the lungs (83.3%). 5 patients (41.7%) had previous chemotherapy, and 4 (33.3%) had previous antiangiogenic therapy. 6 patients (50.0%) had two or more prior lines of treatment before enrollment. As of the September 2023 data cutoff, 2 patients achieved a partial response (PR), 9 had stable disease (SD), yielding a confirmed objective response rate (ORR) of 16.7% (95% confidence interval [CI]: 2.1-48.4%), and a disease control rate (DCR) of 91.7% (95% CI: 61.5-99.8%). The median progression-free survival (PFS) was 8.57 months (95% CI 4.76-11.33), with 3-month and 6-month PFS rates of 83.3% (95% CI: 51.6-97.9%) and 41.7% (95% CI 15.2-72.3%), respectively. Median overall survival (OS) was immature. Most treatment-related adverse events (TRAEs) were grade 1-2, including hyperuricemia (58.3%), hypertension (41.7%). The most common grade ≥3 AEs were hypertension (25.0%), proteinuria (25.0%), and nephrotic syndrome (8.3%). There were no treatment-related deaths. This trial demonstrated that surufatinib showed promising antitumor activity in patients with R/M MSGTs. The safety profile observed in this study aligned with prior clinical studies, requiring continued monitoring and management. [ABSTRACT FROM AUTHOR]