AUTHOR=Rieke Damian T. , Schröder Sebastian , Schafhausen Philippe , Blanc Eric , Zuljan Erika , von der Emde Benjamin , Beule Dieter , Keller Ulrich , Keilholz Ulrich , Klinghammer Konrad 

TITLE=Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1107134

DOI=10.3389/fonc.2023.1107134

ISSN=2234-943X

ABSTRACT=<sec><title>Background and purpose</title><p>A subgroup of salivary duct carcinoma (SDC) harbor overexpression of the androgen receptor (AR), and co-occurring mutations in the <italic>HRAS</italic>- and <italic>PIK3CA</italic>-genes. The impact of genomic complexity on targeted treatment strategies in advanced cancer is unknown.</p></sec><sec><title>Materials and methods</title><p>We analyzed molecular and clinical data from an institutional molecular tumor board (MTB) to identify AR+, <italic>HRAS</italic>/<italic>PIK3CA</italic> co-mutated SDC. Follow-up was performed within the MTB registrational study or retrospective chart review after approval by the local ethics committee. Response was assessed by the investigator. A systematic literature search was performed in MEDLINE to identify additional clinically annotated cases.</p></sec><sec><title>Results</title><p>4 patients with AR+ <italic>HRAS</italic>/<italic>PIK3CA</italic> co-mutated SDC and clinical follow-up data were identified from the MTB. An additional 9 patients with clinical follow-up were identified from the literature. In addition to AR overexpression and <italic>HRAS</italic> and <italic>PIK3CA</italic>-alterations, PD-L1 expression and Tumor Mutational Burden &gt; 10 Mutations per Megabase were identified as additional potentially targetable alterations. Among evaluable patients, androgen deprivation therapy (ADT) was initiated in 7 patients (1 Partial Response (PR), 2 Stable Disease (SD), 3 Progressive Disease (PD), 2 not evaluable), tipifarnib was initiated in 6 patients (1 PR, 4 SD, 1 PD). One patient each was treated with immune checkpoint inhibition (Mixed Response) and combination therapies of tipifarnib and ADT (SD) and alpelisib and ADT (PR).</p></sec><sec><title>Conclusion</title><p>Available data further support comprehensive molecular profiling of SDC. Combination therapies, PI3K-inhibitors and immune therapy warrant further investigation, ideally in clinical trials. Future research should consider this rare subgroup of SDC.</p></sec>