Excellent Response With Alpelisib and Bicalutamide for Advanced Salivary Duct Carcinoma With PIK3CA Mutation and High Androgen Receptor Expression—A Case Report

Sheth, Hardik; Kumar, Prashant; Shreenivas, Aditya; Sambath, Janani; Pragya, Ramya; Madre, Chetan; Athikari, Nevitha; Khandare, Hemant; Peshattiwar, Vishal; Datar, Rajan; Limaye, Sewanti

doi:10.1200/po.20.00436

Cited by 10 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, in non-ACC SGC, the evidence level is 3a based on the efficacy of PIK3CA inhibitors in breast cancer [ 43 ]. One case of apelisib plus androgen deprivation in SDC is reported, resulting in significant benefits [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer

Rack

Feeney

Hapuarachi

et al. 2022

Cancers

View full text Add to dashboard Cite

For most patients with salivary gland cancer, there are no effective standard systemic therapies. Although clinical trials of biomarker-led drug therapies have delivered significant recent advances, there remains a need to understand the clinical utility of genomic profiling of cancer as a means to match patients with recurrent or metastatic salivary gland cancer to clinical trial therapies. In total, 209 patients with salivary gland cancers were profiled with 24 gene (n = 209)) and >325 gene (n = 32) DNA-based next-generation sequencing panels. A retrospective systematic evaluation was performed to identify the frequency of available matched drug therapies within clinical trials based on the results. The matches were then stratified based upon the level of evidence supporting the drug–biomarker combination being investigated using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT) to determine the strength of the clinical rationale for each gene–drug match identified. DNA-based next generation sequencing (NGS) analysis was successful in 175/209 (84%) patients with salivary gland cancer. Using the 24-gene NGS panel, actionable alterations were identified in 27% (48/175) patients. Alterations were most frequent in salivary duct carcinoma (88%) characterized by TP53 and/or PIK3CA mutations, with matched trials available for 63% (10/16). In ACC, biomarker-matched trials were available for 7% (8/115), and no genomic alterations were found in 96/115 (83%) of ACC patients. TP53 was the most frequently altered gene across all subtypes; however, there were no trials recruiting based on TP53 status. In 32 ACC patients with no genomic alterations using the 24-gene panel, a broader (>325 gene) panel identified alterations in 87% (27/32) of cases with biomarker-matched trials available in 40% (13/32) cases. This study identified that genomic profiling using focused (24-gene) NGS panels has potential utility in matching to trial therapies for most patients with non-ACC salivary gland cancer. For patients with ACC, broader genomic profiling has demonstrated added clinical utility. We describe the application of an approach to classification of levels of evidence which may be helpful to inform the clinician and patient decision making around the selection of clinical trial therapies.

show abstract

Section: Resultsmentioning

confidence: 99%

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer

Rack

Feeney

Hapuarachi

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…No major (common terminology criteria of adverse events, CTCAE grade 4 or higher) or unexpected toxicities were observed in the 4 patients identified from the MTB database and no dose reductions were required. In published data, a dose reduction because of toxicity was required in six patients (46%) receiving tipifarnib (4 because of cytopenia, 2 because of reversible renal failures), hypoglycemia requiring dose reduction was reported for alpelisib ( 9 , 21 ). Toxicity data were not reported in the literature for patients receiving antiandrogen therapy in this cohort ( 22 , 23 ).…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2023

View full text Add to dashboard Cite

Background and purposeA 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 methodsWe 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.Results4 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).ConclusionAvailable 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.

show abstract

“…Several cancers show PIK3CA gene mutations and these mutations make them therapeutic targets [ 26 , 30 , 31 ]. To better understand the potential mechanisms, more research is still needed.…”

Section: Discussionmentioning

confidence: 99%

A Rare Pathological Phenotype of Endometrioid Serous and Clear-Cell Ovarian Cancer with PIK3CA Mutations in Relation to The Excellent Response of Alpelisib

Bayram

Khatib

Güney

et al. 2023

Genes

View full text Add to dashboard Cite

Patients with metastatic ovarian cancer who develop resistance to standard therapy with or without platinum need to search for other therapeutic choices. Therefore, identifying genetic alterations and selecting an approach to treatment using precision medicine techniques are important. In a patient diagnosed with mixed-type ovarian cancer after surgery, adjuvant therapy was applied with a combination of carboplatin and taxane, but the disease recurred. Upon evaluation of the patient as having platinum-sensitive epithelial ovarian cancer (EOC), combination therapy with bevacizumab was initially successful. However, disease progression was again observed, and molecular analysis revealed the presence of an E545K mutation in the PIK3CA gene; therefore, a selective PI3K inhibitor, alpelisib, was used as a treatment under the compassionate-use protocol. The patient’s complications improved after receiving the alpelisib medication. The patient has been in complete remission for over two years. This case serves as a rare example that confirms the utility of alpelisib in managing mixed-type ovarian cancer.

show abstract

Excellent Response With Alpelisib and Bicalutamide for Advanced Salivary Duct Carcinoma With PIK3CA Mutation and High Androgen Receptor Expression—A Case Report

Cited by 10 publications

References 26 publications

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer

Evaluation of the Clinical Utility of Genomic Profiling to Inform Selection of Clinical Trial Therapy in Salivary Gland Cancer

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

A Rare Pathological Phenotype of Endometrioid Serous and Clear-Cell Ovarian Cancer with PIK3CA Mutations in Relation to The Excellent Response of Alpelisib

Contact Info

Product

Resources

About