AbstractBackgroundTreatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all‐trans retinoic acid (ATRA) combined with low‐dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study.MethodsPatients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment‐related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2/day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD).ResultsA total of 16 patients were included with nine (56.3%) males and aged 35–69 years old. All recruited patients previously received anti‐angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow‐up of 23.9 months (range:17.8–31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression‐free survival (PFS) was 16.3 months (95% CI: 7.2–25.4 months), and the 6‐month, 12‐month, and 24‐month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n= 2, 12.5%) and hand‐foot syndrome (n= 1, 6.25%).ConclusionAll‐trans retinoic acid combined with low‐dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT 04433169).