6026 Background: There is no standard treatment for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). Moreover, MYB and/or NOTCH1 mutation can lead to worse prognosis. Currently, anti-angiogenic targeted therapy is a relatively effective treatment option, but the accompanied toxicities may hinder the continuous medication. All-trans retinoic acid (ATRA) induces differentiation and promotes apoptosis, enhancing the cytotoxicity of anti-tumor agents; on the other hand, inhibits c-MYB and/or NOTCH1 expression. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We reported the preliminary results of the efficacy and safety of ATRA combined with low-dose apatinib in patients with R/M ACC. Methods: In this exploratory study, patients with pathologically or histologically confirmed advanced, R/M ACC with measurable disease were screened. Patients who previously received anti-angiogenic therapy then withdrew due to toxicities could be recruited. ATRA was administered orally at a dose of 20 mg twice a day, and apatinib was administered orally at a dose of 250 mg once a day. The primary endpoint was objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors v1.1. Results: Between March 2019 and April 2020, a total of 16 patients were enrolled. The median age was 53 years (range: 35-69), and 7 (44%) patients were male. Four (25%) patients received ATRA plus apatinib as the third-line therapy, while 12 (75%) received as the second-line therapy. Of 16 patients, 3 (19%) achieved partial response and 13 (81%) achieved stable disease (SD), with ORR of 19% and disease control rate of 100%, respectively. Among patients with SD, 12 (75%) showed tumor shrinkage (3%-28%) and 1 (6%) showed minor tumor enlargement (2%). The median follow-up time was 14.5 months (range: 8.1-22.1). Throughout the period, 5 (42%) patients developed disease progression. The 6-month and 12-month progression-free survival rates were 100% and 80%, respectively. Grade 3 adverse events included hand-foot syndrome (1 [6%]) and proteinuria (1 [6%]). No grade ≥4 adverse events occurred. Conclusions: ATRA combined with low-dose anti-angiogenic drug apatinib could be a potential treatment option for patients with R/M ACC, including those with pretreated advanced ACC after progression on or intolerance to other therapies. These encouraging results were worth further investigations, and a randomized phase 2 trial in ongoing (the Aplus study, NCT04433169).
all-trans retinoic acid for treating germ cell tumors. In vitro activity and results of a phase II trial
