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

TY - JOUR

T1 - Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma

AU - Rieke, Damian T

AU - Schröder, Sebastian

AU - Schafhausen, Philippe

AU - Blanc, Eric

AU - Zuljan, Erika

AU - von der Emde, Benjamin

AU - Beule, Dieter

AU - Keller, Ulrich

AU - Keilholz, Ulrich

AU - Klinghammer, Konrad

N1 - Copyright © 2023 Rieke, Schröder, Schafhausen, Blanc, Zuljan, von der Emde, Beule, Keller, Keilholz and Klinghammer.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

U2 - 10.3389/fonc.2023.1107134

DO - 10.3389/fonc.2023.1107134

M3 - SCORING: Journal article

C2 - 37427101

VL - 13

SP - 1107134

JO - FRONT ONCOL

JF - FRONT ONCOL

SN - 2234-943X

ER -