b622d3ef3498e04967ab116a08b3a26e pmc_11431065.pdf 564cb9eaa42fc6818cfda7bebe696c3b097736b5 pmc_11431065.pdf 32e6bb98299625e6b1508fe1dae3dde833c366b9400607157b5df87803f04146 pmc_11431065.pdf Title: The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers Subject: Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan–Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0–47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group. Keywords: salivary gland cancer; HER2; trastuzumab; TDM1; ado-trastuzumab emtansine; trastuzumab deruxtecan Author: Joseph Edward Haigh, Karan Patel, Sam Rack, Pablo Jiménez-Labaig, Guy Betts, Kevin Joseph Harrington and Robert Metcalf Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sat Sep 21 03:35:08 2024 CEST ModDate: Sat Sep 21 03:39:39 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1217851 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 HKQBXB+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 ODOOCL+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 POYAAW+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 BAMNYG+VnURWPalladioL Type 1 Custom yes yes yes 32 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 81 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 85 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 89 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 93 0 BCDJEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 100 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 112 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 116 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 120 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 124 0 BCDJEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 131 0 DVCMRV+CMSY10 Type 1 Builtin yes yes yes 143 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 152 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 156 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 160 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 164 0 BCDJEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 171 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:47:54 CET RepresentationInformation: pmc_11431065.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-01-25 02:29:57 CET Size: 1217851 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 268 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers Author: Joseph Edward Haigh, Karan Patel, Sam Rack, Pablo Jiménez-Labaig, Guy Betts, Kevin Joseph Harrington and Robert Metcalf Subject: Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0 47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group. 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