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

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

doi:10.3389/fonc.2023.1107134

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

Front Oncol. 2023 Jun 20:13:1107134. doi: 10.3389/fonc.2023.1107134. eCollection 2023.

Authors

Damian T Rieke^{1

2

3

4}, Sebastian Schröder¹, Philippe Schafhausen⁵, Eric Blanc^{3

6}, Erika Zuljan^{3

6}, Benjamin von der Emde¹, Dieter Beule^{3

6}, Ulrich Keller^{1

4

7}, Ulrich Keilholz^{2

4}, Konrad Klinghammer^{1

4}

Affiliations

¹ Department of Hematology, Oncology and Cancer Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
³ Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁴ German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵ Department of Oncology, Hematology, and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Core Unit Bioinformatics (CUBI), Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁷ Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.

Abstract

Background and purpose: A subgroup of salivary duct carcinoma (SDC) harbor overexpression of the androgen receptor (AR), and co-occurring mutations in the HRAS- and PIK3CA-genes. The impact of genomic complexity on targeted treatment strategies in advanced cancer is unknown.

Materials and methods: We analyzed molecular and clinical data from an institutional molecular tumor board (MTB) to identify AR+, HRAS/PIK3CA 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.

Results: 4 patients with AR+ HRAS/PIK3CA 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 HRAS and PIK3CA-alterations, PD-L1 expression and Tumor Mutational Burden > 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).

Conclusion: 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.

Keywords: head and neck cancer; molecular tumor board; precision oncology; salivary duct carcinoma; salivary gland cancer; targeted therapy.

Grants and funding

DR is a participant in the Berlin Institute of Health – Charité Clinical Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. We acknowledge financial support from the Open Access Publication Fund of Charité – Universitätsmedizin Berlin and the German Research Foundation (DFG).