Molecular Subtype-Associated Response to Cyclophosphamide-Epirubicin-Cisplatin Regimen in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Retrospective Single-Center Study.

Recurrent or metastatic adenoid cystic carcinoma (R/M ACC) has no standard systemic therapy. VEGFR-targeting tyrosine kinase inhibitors (TKIs) are commonly used first-line, though no international standard exists; cisplatin-based chemotherapy is an alternative. We retrospectively reviewed the cyclophosphamide-epirubicin-cisplatin (CEP) regimen to determine whether prior TKI exposure compromises subsequent chemotherapy efficacy. We studied 31 patients given CEP for progressive R/M ACC (2018-2023). Tumor response was assessed by RECIST 1.1. Molecular subtype was determined by c-MYC/p63 immunohistochemistry (ACC-I, c-MYC-positive/p63-negative; ACC-II, p63-positive/c-MYC-low or negative). Multivariable models used Firth's penalized likelihood Cox regression. Next-generation sequencing (NGS) was available in 21 of 31 patients. Thirty-one patients were enrolled (median age 48; 17 [54.8%] with prior TKI). At median follow-up of 22.6 months, the objective response rate (ORR) was 19.4%, disease control rate 71.0%, median progression-free survival (PFS) 5.3 months, and median overall survival (OS) 10.3 months. Prior TKI did not lower efficacy: ORR 17.6% vs. 21.4%, PFS hazard ratio 0.76 (p = 0.519). All six partial responses occurred in ACC-I tumors (35.3% vs. 0% in ACC-II, p = 0.021). In the NGS subset (5 PIK3CA-mutant), PIK3CA mutation (OS HR 6.19, p = 0.024) and bone metastasis (OS HR 5.84, p = 0.027) remained associated with shorter OS after adjustment. No treatment-related deaths occurred. CEP is active in R/M ACC, and prior TKI exposure did not appear to reduce efficacy. Higher response rates in ACC-I tumors and the apparent PIK3CA-related survival deficit are exploratory observations that need prospective testing before they can guide treatment.