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•ACC patients treated within 3 years of recurrent, metastatic diagnosis have poor outcomes.•Disease biology drives prognosis in ACC, despite the use of systemic therapy for advanced disease.•PI3K pathway alterations identify a subgroup with intermediate prognosis in advanced ACC.•Advanced ACC patients who receive personalized target therapies have favorable response rates.
Little is known about the long-term impact of local and systemic therapies for recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC), or the clinical significance of molecular alterations.
We identified 72 R/M cases among 123 ACC patients from our institution. We report long-term outcomes, predictors of recurrence and survival, and the impact of sequential cancer-directed therapy among R/M patients. We integrate genomic data for 36 sequenced ACC patients.
Median overall survival (OS) from initial diagnosis was 35.1 ys (95%CI: 25.8–37.3) for R/M ACC patients. 10-y OS among R/M patients was 84.7%, worse for patients with extra-pulmonary metastatic disease (p = 0.02). Only initial disease stage predicted recurrence (OR 1.69, p = 0.03). Longer time to first R/M treatment predicted improved survival (p < 0.01); those treated ≤ 3 years from their R/M diagnosis had poor outcomes (p = 0.01). R/M patients who received systemic therapy vs. active surveillance had similar survival (p = 0.35). Molecular findings predicted outcomes: 10-y OS: 100% MYB, 53.3% PI3K, 32.1% NOTCH1 and others, p = 0.03. PI3K mutations predicted a longer disease-free interval (p = 0.04).
Underlying disease biology remains the strongest predictor of outcomes in R/M ACC. Shorter time to R/M therapy predicts poor outcomes. Molecular alterations are prognostic, and PI3K mutations identify an intermediate-risk ACC subgroup.