PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要：
■唾液导管癌（SDC）的一个亚组有雄激素受体（AR）的过表达，以及HRAS和PIK3CA基因中的共同突变。基因组复杂性对晚期癌症靶向治疗策略的影响尚不清楚。
■我们分析了来自机构分子肿瘤委员会（MTB）的分子和临床数据，以确定AR+，HRAS/PIK3CA共突变的SDC。在当地伦理委员会批准后，在MTB注册研究或回顾性图表审查中进行随访。研究者评估了反应。在MEDLINE中进行了系统的文献检索，以确定其他临床注释病例。
■从MTB中确定了4例AR+HRAS/PIK3CA共突变SDC患者和临床随访数据。从文献中确定了另外9例进行临床随访的患者。除了AR过表达和HRAS和PIK3CA改变，PD-L1表达和肿瘤突变负担>10个突变每个兆糖酶被鉴定为另外的潜在可靶向改变。在可评估的患者中，7例患者开始雄激素剥夺治疗（ADT）（1部分缓解（PR），2稳定疾病（SD），3进行性疾病（PD），2不可评估)，6例患者开始使用替比法尼(1例PR，4SD,1PD)。一名患者分别接受免疫检查点抑制（混合反应）以及替比法尼和ADT（SD）以及alpelisib和ADT（PR）的联合治疗。
■现有数据进一步支持SDC的全面分子谱分析。联合疗法,PI3K抑制剂和免疫治疗需要进一步研究，理想的临床试验。未来的研究应考虑SDC的这一罕见亚组。
■我们分析了来自机构分子肿瘤委员会（MTB）的分子和临床数据，以确定AR+，HRAS/PIK3CA共突变的SDC。在当地伦理委员会批准后，在MTB注册研究或回顾性图表审查中进行随访。研究者评估了反应。在MEDLINE中进行了系统的文献检索，以确定其他临床注释病例。
■从MTB中确定了4例AR+HRAS/PIK3CA共突变SDC患者和临床随访数据。从文献中确定了另外9例进行临床随访的患者。除了AR过表达和HRAS和PIK3CA改变，PD-L1表达和肿瘤突变负担>10个突变每个兆糖酶被鉴定为另外的潜在可靶向改变。在可评估的患者中，7例患者开始雄激素剥夺治疗（ADT）（1部分缓解（PR），2稳定疾病（SD），3进行性疾病（PD），2不可评估)，6例患者开始使用替比法尼(1例PR，4SD,1PD)。一名患者分别接受免疫检查点抑制（混合反应）以及替比法尼和ADT（SD）以及alpelisib和ADT（PR）的联合治疗。
■现有数据进一步支持SDC的全面分子谱分析。联合疗法,PI3K抑制剂和免疫治疗需要进一步研究，理想的临床试验。未来的研究应考虑SDC的这一罕见亚组。
