Treatment patterns and systemic therapy outcomes for patients with salivary duct carcinoma and adenocarcinoma NOS.
Authors: Sousa Luana Guimarães , Wang Kaiwen , Torman Danice , Binks Bailee , Andersen Clark , Lewis Whitney E , Rivera Melvin , Kaya Diana , El-Naggar Adel K. , Hanna Ehab Y. , Esmaeli Bita , Frank Steven J. , Bell Diana , Glisson Bonnie S. , Rodon Ahnert Jordi , Meric-Bernstam Funda , Lee J. Jack , Ferrarotto Renata 
Published: June 2021

6084

Background: Salivary duct carcinoma (SDC) and adenocarcinoma, not otherwise specified (Adeno-NOS) are rare and aggressive subtypes of salivary gland cancers. Biomarker studies revealed targetable alterations such as androgen receptor (AR) and HER2 overexpression; nevertheless, chemotherapy (CT) remains the cornerstone treatment of patients (pts) with locally advanced or metastatic disease based on limited efficacy data. We sought to describe the treatment patterns and outcomes of SDC and Adeno-NOS pts. Methods: We retrospectively collected clinicopathological, treatment, and outcomes data of SDC or Adeno-NOS pts that were seen at MD Anderson from 1990-2020. AR positivity was defined by IHC staining in ≥ 10% of tumor cells, and HER2 by IHC 2+ or 3+ scores. Overall response rate (ORR) was assessed by an independent radiologist per RECIST v1.1. Recurrence-free survival (RFS) and overall survival (OS) from diagnosis were estimated using log-rank test. A multivariable cox regression model was performed to estimate the hazard-ratio (HR) of risk factors on pts outcomes. Results: 200 pts were included, 110 had SDC and 90 Adeno-NOS. Most pts (61%) presented with locoregional disease (stage III-IVB), while 13% had distant metastasis (IVC). AR was positive in 77% of cases, and HER2 in 47%. In the curative setting (N=174), 98% pts underwent surgery and 90% radiotherapy (RT); 15 pts with stage IVA-B disease had aggressive trimodality therapy including surgery, RT, and systemic therapy. Overall, 55% pts recurred. The mRFS and 5-y RFS rate were 24 mos (95%CI, 16-43) and 34.5%, respectively. For pts with IV-A-B stage, trimodality therapy was associated with an improved OS in comparison to surgery and/or RT (39 mos vs NA, p=0.04). In the metastatic setting, 82 pts received ≥1 line of systemic therapy; the preferred 1st line regimen was platinum/taxane with or without trastuzumab (50%). Table summarizes the ORR and mPFS to each therapy line. ORR and PFS was higher for HER2-targeted therapy (1st line: 47% and 11 mos; 2nd line 29% and 6 mos; respectively); only 10 pts received androgen blockage. At a median follow-up of 7.5 y, the mOS was 5 ys and the 5-y OS rate was 50%. In multivariate analysis, higher T and N stages (HR 2.1 and 3.8, p<0.05), and positive margins (HR 2.0, p=0.003) were associated with worse RFS; older age (HR 1.03, p=0.003), and higher TNM stage (HR 1.78, p=0.006) were associated with worse OS. HER2 expression was not prognostic. Conclusions: This study validates prognostic factors in SDC and adeno-NOS and is the largest series to report outcomes to palliative systemic therapy per treatment line, providing a benchmark for future studies in these diseases. Aggressive trimodality therapy may improve outcomes of pts with stage IVA-B disease.[Table: see text]