DISCUSSION
PD
MALIGNANT TUMORS
Treatment options are limited for R/M ACC.All‐trans retinoic acid serves as an attractive candidate for various malignant tumors.This study reviewed 16 patients of R/M ACCHN previously received apatinib monotherapy and then added ATRA therapy. By the last follow‐up date, 12 patients were PD within a range of 17.8–31.7 months of follow‐up. The 6‐month, 12‐month, and 24‐month PFS rates were 100%, 81.3%, and 33.3%, respectively. Comparatively, in the previous study of monotherapy of apatinib with a dosage of 500 mg/day, the 12‐month PFS were 75.2%.Currently, a one‐armed study (NCT03999684) of short‐term ATRA monotherapy (45 mg/mAll patients of this study came from a single center and the sample size is a little bit small; and the treatment and severity of the patients might be a large confounder of this study, therefore, further large‐scale well‐designed study are warrant. Also, the retrospective nature might provide several information bias and limitation. On the other hand, the MYB status and pathological types were unclear since the surgical specimens have exceeded the time for further testing. However, this was the first study summarizing the treatment status of patients with R/M ACCHN which provided the critical information on the combination use of ATRA and apatinib. Above shortages will be perfected in the ongoing trial.All‐trans retinoic acid combined with low‐dose apatinib in patients with R/M ACCHN shows an acceptable efficacy in terms of response and progression‐free survival. Additionally, the reduced‐dose apatinib plus ATRA exhibits an acceptable safety profile, and that the synergistic effects of ATRA plus apatinib may enable reduction in apatinib dose. ATRA combined with apatinib might be a potential treatment option and its efficacy and safety warrant further examined in well‐designed clinical trials. The ongoing clinical trial (NCT04433169) might soon provide more answers regarding the benefits of monotherapy and combination therapy of ATRA for ACC treatment.