Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate (ADC) therapy.

person Lu Si Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China info_outline Lu Si, Jia Jia, Lili Mao, Jing Lin, Pei Yuan, Wen Yu Li, Jie Dai, Zhong-Wu Li, Xue Bai, Caili Li, Lei Guo, Yu Chen, Jianming Ying, Jun Guo

Authors person Lu Si Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China info_outline Lu Si, Jia Jia, Lili Mao, Jing Lin, Pei Yuan, Wen Yu Li, Jie Dai, Zhong-Wu Li, Xue Bai, Caili Li, Lei Guo, Yu Chen, Jianming Ying, Jun Guo Organizations Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital, Beijing, China, Department of Medical Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China, Beijing, China, Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China, Pathology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China Abstract Disclosures Research Funding Other Foundation Beijing Medical Award Foundation (YXJL-2020-0889-0106), Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20220901) Background: Evaluation of HER2 status in extramammary Paget disease (EMPD) has been reported in a few studies with a small number of samples, and the HER2 overexpression rate ranges from 15% to 60%. The prognosis of advanced EMPD is poor and the treatment options is limited. Disitamab Vedotin (DV) is a novel humanized anti-HER2 antibody-drug conjugate (ADC), has been approved for metastatic urothelial carcinoma and gastric cancer in China. To determine the HER2 status and the efficacy of DV in advanced EMPD patients (pts) harboring HER2 expression, we conducted this multicenter retrospective study. Methods: Paraffin-embedded blocks, clinic-pathological data, and survival data of EMPD pts were retrospectively collected from 3 centers in China. HER2 IHC scoring and gene amplification evaluation were carried out according to the (ASCO/CAP) 2018 guidelines. The results of FISH and IHC were analyzed by two pathologists independently in a double-blinded manner. Data analysis was performed using SPSS v.26, Prism 8 and R version 3.6.5. Results: Finally, 129 cases with detailed data were enrolled between 2006 and 2022. Among them, HER2 IHC was performed in 102 cases, and FISH in 46 cases. HER2 expression was detected in 93.1% samples, with scores of 1+, 2+, and 3+ in 47.1% (48/102), 37.3% (38/102), and 8.7% (9/102) respectively. HER2 gene amplification was detected in eight cases (8/46, 17.4%), including all the cases with IHC 3+ (5/5, 100%), two with IHC 2+ (2/18, 11.1%), and one with IHC 1+ (1/22, 4.5%). For the subgroup of HER2 2+/3+, a higher frequency of lymph node metastasis (66.7% vs 33.3%, P = 0.034) and reduced survival time were detected than in HER2 1+/0. Two elderly male pts with advanced EMPD (one HER1+ /FISH-, one HER 2+/FISH-), who failed with chemo of paclitaxel, received 4 doses of DV infusion (2mg/kg every 2 weeks), and achieved partial responses both with tolerable toxicity. Conclusions: According to the study, the expression rate of HER-2 was very high in EMPD, indicating that it may be used as a routine treatment target. DV showed efficacy in these patients and need further validation.