{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T08:56:46Z","timestamp":1770713806081,"version":"3.49.0"},"reference-count":32,"publisher":"Harborside Press, LLC","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Trastuzumab deruxtecan (T-DXd) has shown efficacy in HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+\/in situ hybridization [ISH]+) recurrent\/metastatic (R\/M) secretory gland cancers of the head and neck. However, there are minimal published data regarding the use of T-DXd in HER2-low (IHC 1+ or IHC 2+\/ISH\u2212) or\n HER2<\/jats:italic>\n -mutant tumors. This case series aimed to describe the clinical characteristics and outcomes of patients with HER2-low or\n HER2<\/jats:italic>\n -mutant R\/M salivary gland cancer (SGC) or lacrimal gland cancer (LGC) who received T-DXd in any line of therapy. Patients included in this series had a confirmed diagnosis of SGC or LGC, were evaluated at the MD Anderson Head and Neck Center, and received at least one dose of T-DXd. HER2 status was evaluated according to ASCO\/CAP guidelines for breast cancer as recommended by NCCN.\n HER2<\/jats:italic>\n -activating mutations were identified with tissue-based next-generation sequencing. Best overall response to T-DXd per RECIST v1.1 was evaluated for patients with adequate imaging and measurable disease. The final cohort comprised 9 patients (SGC, n=8; LGC, n=1), including 7 with HER2-low and 2 with\n HER2<\/jats:italic>\n -mutant tumors. T-DXd was given off-label in 7 patients; 2 received T-DXd on a clinical trial. Among 6 patients who were eligible for RECIST, 4 (66.7%) had a partial response, including 1 complete response in target lesions. The 3 patients who were not eligible for RECIST had oncologist-documented clinical and\/or radiographic improvement. The median time on T-DXd among all patients was 8.9 months. T-DXd demonstrated promising and durable antitumor activity. This antibody\u2013drug conjugate should be considered a viable therapeutic option for HER2-low and\n HER2<\/jats:italic>\n -mutant R\/M SGC\/LGC, with potential use in the frontline setting when preferred systemic therapies are unavailable.\n <\/jats:p>","DOI":"10.6004\/jnccn.2025.7104","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T16:28:03Z","timestamp":1762792083000},"source":"Crossref","is-referenced-by-count":0,"title":["Trastuzumab Deruxtecan in HER2-Low or HER2-Mutant Recurrent\/Metastatic Secretory Gland Cancers of the Head and Neck: A Case Series"],"prefix":"10.6004","volume":"24","author":[{"given":"Michael T.","family":"Wotman","sequence":"first","affiliation":[{"name":"Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura L.","family":"Gillison","sequence":"additional","affiliation":[{"name":"Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neal","family":"Akhave","sequence":"additional","affiliation":[{"name":"Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Kerrigan","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Ferrarotto","sequence":"additional","affiliation":[{"name":"Thoracic\/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4047","reference":[{"key":"B1","series-title":"Expert Rev Anticancer Ther","first-page":"573","article-title":"Targeting human EGFR 2 (HER2) in salivary gland carcinoma","volume":"23","author":"Wotman M","year":"2023","unstructured":"Wotman M, El-Naggar A, Ferrarotto R. Targeting human EGFR 2 (HER2) in salivary gland carcinoma. Expert Rev Anticancer Ther 2023;23:573\u2013582."},{"key":"B2","series-title":"Jpn J Clin Oncol","first-page":"434","article-title":"Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies","volume":"54","author":"Takahashi S","year":"2024","unstructured":"Takahashi S, Bando H, Kinoshita I, Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol 2024;54:434\u2013443."},{"key":"B3","series-title":"Ann Oncol","first-page":"S613","article-title":"849O: Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent\/metastatic salivary gland cancer: results from the MYTHOS trial","volume":"35","author":"Kinoshita I","year":"2024","unstructured":"Kinoshita I, Kano S, Honma Y, 849O: Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent\/metastatic salivary gland cancer: results from the MYTHOS trial. Ann Oncol 2024;35:S613\u2013614."},{"key":"B4","series-title":"J Clin Oncol","first-page":"47","article-title":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial","volume":"42","author":"Meric-Bernstam F","year":"2024","unstructured":"Meric-Bernstam F, Makker V, Oaknin A, Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42:47\u201358."},{"key":"B5","series-title":"N Engl J Med","first-page":"9","article-title":"Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer","volume":"387","author":"Modi S","year":"2022","unstructured":"Modi S, Jacot W, Yamashita T, Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387:9\u201320."},{"key":"B6","series-title":"N Engl J Med","first-page":"241","article-title":"Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","volume":"386","author":"Li BT","year":"2022","unstructured":"Li BT, Smit EF, Goto Y, Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 2022;386:241\u2013251."},{"key":"B7","series-title":"J Clin Oncol","article-title":"Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial","author":"Goto K","unstructured":"Goto K, Goto Y, Kubo T, Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial. J Clin Oncol 2023;41:4852\u20134863."},{"key":"B8","series-title":"Lancet Oncol","first-page":"707","article-title":"Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study","volume":"25","author":"Li BT","year":"2024","unstructured":"Li BT, Meric-Bernstam F, Bardia A, Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol 2024;25:707\u2013719."},{"key":"B9","article-title":"NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2025","author":"Pfister","unstructured":"Pfister DG, Spencer S, Adkins D, . NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2025. Accessed December 23, 2024. To view the most recent version, visit https:\/\/www.nccn.org"},{"key":"B10","series-title":"Expert Opin Investig Drugs","first-page":"851","article-title":"Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate","volume":"33","author":"Edoardo C","year":"2024","unstructured":"Edoardo C, Giuseppe C. Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate. Expert Opin Investig Drugs 2024;33:851\u2013865."},{"key":"B11","series-title":"Chem Pharm Bull (Tokyo)","first-page":"173","article-title":"The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy","volume":"67","author":"Nakada T","year":"2019","unstructured":"Nakada T, Sugihara K, Jikoh T, The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo) 2019;67:173\u2013185."},{"key":"B12","series-title":"Clin Cancer Res","first-page":"5097","article-title":"DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1","volume":"22","author":"Ogitani Y","year":"2016","unstructured":"Ogitani Y, Aida T, Hagihara K, DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res 2016;22:5097\u20135108."},{"key":"B13","series-title":"Cancer Discov","first-page":"674","article-title":"HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers","volume":"10","author":"Li BT","year":"2020","unstructured":"Li BT, Michelini F, Misale S, HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers. Cancer Discov 2020;10:674\u2013687."},{"key":"B14","series-title":"Cancer","first-page":"4380","article-title":"Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers","volume":"125","author":"Offin M","year":"2019","unstructured":"Offin M, Feldman D, Ni A, Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers. Cancer 2019;125:4380\u20134387."},{"key":"B15","series-title":"Target Oncol","first-page":"705","article-title":"Trastuzumab-deruxtecan: redefining HER2 as a tumor agnostic biomarker","volume":"19","author":"Zouein J","year":"2024","unstructured":"Zouein J, Karam E, Strickler JH, Kourie HR. Trastuzumab-deruxtecan: redefining HER2 as a tumor agnostic biomarker. Target Oncol 2024;19:705\u2013710."},{"key":"B16","series-title":"Nat Med","first-page":"3780","article-title":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b\/4 trial","volume":"30","author":"Harbeck N","year":"2024","unstructured":"Harbeck N, Ciruelos E, Jerusalem G, Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b\/4 trial. Nat Med 2024;30:3780."},{"key":"B1","series-title":"Expert Rev Anticancer Ther","first-page":"573","article-title":"Targeting human EGFR 2 (HER2) in salivary gland carcinoma","volume":"23","author":"Wotman M","year":"2023","unstructured":"Wotman M, El-Naggar A, Ferrarotto R. Targeting human EGFR 2 (HER2) in salivary gland carcinoma. Expert Rev Anticancer Ther 2023;23:573\u2013582."},{"key":"B2","series-title":"Jpn J Clin Oncol","first-page":"434","article-title":"Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies","volume":"54","author":"Takahashi S","year":"2024","unstructured":"Takahashi S, Bando H, Kinoshita I, Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2-expressing salivary gland carcinoma: a pooled analysis of two phase I studies. Jpn J Clin Oncol 2024;54:434\u2013443."},{"key":"B3","series-title":"Ann Oncol","first-page":"S613","article-title":"849O: Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent\/metastatic salivary gland cancer: results from the MYTHOS trial","volume":"35","author":"Kinoshita I","year":"2024","unstructured":"Kinoshita I, Kano S, Honma Y, 849O: Phase II study of trastuzumab deruxtecan in patients with HER2-positive recurrent\/metastatic salivary gland cancer: results from the MYTHOS trial. Ann Oncol 2024;35:S613\u2013614."},{"key":"B4","series-title":"J Clin Oncol","first-page":"47","article-title":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial","volume":"42","author":"Meric-Bernstam F","year":"2024","unstructured":"Meric-Bernstam F, Makker V, Oaknin A, Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol 2024;42:47\u201358."},{"key":"B5","series-title":"N Engl J Med","first-page":"9","article-title":"Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer","volume":"387","author":"Modi S","year":"2022","unstructured":"Modi S, Jacot W, Yamashita T, Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387:9\u201320."},{"key":"B6","series-title":"N Engl J Med","first-page":"241","article-title":"Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer","volume":"386","author":"Li BT","year":"2022","unstructured":"Li BT, Smit EF, Goto Y, Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med 2022;386:241\u2013251."},{"key":"B7","series-title":"J Clin Oncol","article-title":"Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial","author":"Goto K","unstructured":"Goto K, Goto Y, Kubo T, Trastuzumab deruxtecan in patients with HER2-mutant metastatic non-small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial. J Clin Oncol 2023;41:4852\u20134863."},{"key":"B8","series-title":"Lancet Oncol","first-page":"707","article-title":"Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study","volume":"25","author":"Li BT","year":"2024","unstructured":"Li BT, Meric-Bernstam F, Bardia A, Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol 2024;25:707\u2013719."},{"key":"B9","article-title":"NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2025","author":"Pfister","unstructured":"Pfister DG, Spencer S, Adkins D, . NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2025. Accessed December 23, 2024. To view the most recent version, visit https:\/\/www.nccn.org"},{"key":"B10","series-title":"Expert Opin Investig Drugs","first-page":"851","article-title":"Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate","volume":"33","author":"Edoardo C","year":"2024","unstructured":"Edoardo C, Giuseppe C. Trastuzumab-deruxtecan in solid tumors with HER2 alterations: from early phase development to the first agnostic approval of an antibody-drug conjugate. Expert Opin Investig Drugs 2024;33:851\u2013865."},{"key":"B11","series-title":"Chem Pharm Bull (Tokyo)","first-page":"173","article-title":"The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy","volume":"67","author":"Nakada T","year":"2019","unstructured":"Nakada T, Sugihara K, Jikoh T, The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo) 2019;67:173\u2013185."},{"key":"B12","series-title":"Clin Cancer Res","first-page":"5097","article-title":"DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1","volume":"22","author":"Ogitani Y","year":"2016","unstructured":"Ogitani Y, Aida T, Hagihara K, DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res 2016;22:5097\u20135108."},{"key":"B13","series-title":"Cancer Discov","first-page":"674","article-title":"HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers","volume":"10","author":"Li BT","year":"2020","unstructured":"Li BT, Michelini F, Misale S, HER2-mediated internalization of cytotoxic agents in ERBB2 amplified or mutant lung cancers. Cancer Discov 2020;10:674\u2013687."},{"key":"B14","series-title":"Cancer","first-page":"4380","article-title":"Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers","volume":"125","author":"Offin M","year":"2019","unstructured":"Offin M, Feldman D, Ni A, Frequency and outcomes of brain metastases in patients with HER2-mutant lung cancers. Cancer 2019;125:4380\u20134387."},{"key":"B15","series-title":"Target Oncol","first-page":"705","article-title":"Trastuzumab-deruxtecan: redefining HER2 as a tumor agnostic biomarker","volume":"19","author":"Zouein J","year":"2024","unstructured":"Zouein J, Karam E, Strickler JH, Kourie HR. Trastuzumab-deruxtecan: redefining HER2 as a tumor agnostic biomarker. Target Oncol 2024;19:705\u2013710."},{"key":"B16","series-title":"Nat Med","first-page":"3780","article-title":"Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b\/4 trial","volume":"30","author":"Harbeck N","year":"2024","unstructured":"Harbeck N, Ciruelos E, Jerusalem G, Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b\/4 trial. Nat Med 2024;30:3780."}],"container-title":["Journal of the National Comprehensive Cancer Network"],"original-title":[],"link":[{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/2\/article-e257104.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/2\/article-e257104.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jnccn.org\/downloadpdf\/journals\/jnccn\/24\/2\/article-e257104.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T13:46:23Z","timestamp":1770644783000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnccn.org\/view\/journals\/jnccn\/24\/2\/article-e257104.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":32,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.6004\/jnccn.2025.7104","relation":{},"ISSN":["1540-1405","1540-1413"],"issn-type":[{"value":"1540-1405","type":"print"},{"value":"1540-1413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]}}}