Human epidermal growth factor receptor-2 (HER2) is a potential therapeutic target in extramammary Paget's disease of the vulva.


Journal

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
ISSN: 1525-1438
Titre abrégé: Int J Gynecol Cancer
Pays: England
ID NLM: 9111626

Informations de publication

Date de publication:
11 2020
Historique:
received: 19 06 2020
revised: 01 09 2020
accepted: 03 09 2020
pubmed: 2 10 2020
medline: 11 11 2021
entrez: 1 10 2020
Statut: ppublish

Résumé

Invasive vulvar Paget's disease with over-expression of the human epidermal growth factor receptor 2 (HER2) protein is potentially suitable for targeted therapy, especially in a metastatic setting where no effective treatments are available. Four consecutive patients with HER2 positive advanced vulvar Paget's disease, treated with weekly trastuzumab (loading dose 4 mg/kg, then 2 mg/kg) and paclitaxel (80 mg/m Median age and follow-up of patients were 62.5 years (45-74) and 16 months (6-54), respectively. Complete or partial responses were observed in all patients. Median time to response was 3 months (range 2-4), while median duration of response was 10 months (range 2-34). Case 1 presented with pulmonary and lymph nodes involvement. She experienced a radiological complete response after 24 treatment administrations, and a progression-free survival of 36 months. At disease progression, treatment re-challenge achieved partial response. She is currently receiving treatment with trastuzumab-emtansine. Case 2 was a 74-year-old woman who developed pulmonary metastasis after first-line cisplatin treatment. She had a partial response and a progression-free survival of 10 months. Case 3 had inguinal and para-aortic lymphadenopathy in complete response after 18 treatment administrations. She developed brain metastasis while receiving trastuzumab maintenance. Case 4 was treated for locally advanced disease and experienced a subjective benefit with relief in perineal pain and itching. No unexpected treatment-related side effects were reported. Advanced vulvar Paget's disease is a rare disorder and no standard treatment is available. In the sub-group of HER2 positive disease, weekly paclitaxel-trastuzumab appears to be active and safe, and may be considered a therapeutic option in these patients.

Sections du résumé

BACKGROUND
Invasive vulvar Paget's disease with over-expression of the human epidermal growth factor receptor 2 (HER2) protein is potentially suitable for targeted therapy, especially in a metastatic setting where no effective treatments are available.
METHODS
Four consecutive patients with HER2 positive advanced vulvar Paget's disease, treated with weekly trastuzumab (loading dose 4 mg/kg, then 2 mg/kg) and paclitaxel (80 mg/m
RESULTS
Median age and follow-up of patients were 62.5 years (45-74) and 16 months (6-54), respectively. Complete or partial responses were observed in all patients. Median time to response was 3 months (range 2-4), while median duration of response was 10 months (range 2-34). Case 1 presented with pulmonary and lymph nodes involvement. She experienced a radiological complete response after 24 treatment administrations, and a progression-free survival of 36 months. At disease progression, treatment re-challenge achieved partial response. She is currently receiving treatment with trastuzumab-emtansine. Case 2 was a 74-year-old woman who developed pulmonary metastasis after first-line cisplatin treatment. She had a partial response and a progression-free survival of 10 months. Case 3 had inguinal and para-aortic lymphadenopathy in complete response after 18 treatment administrations. She developed brain metastasis while receiving trastuzumab maintenance. Case 4 was treated for locally advanced disease and experienced a subjective benefit with relief in perineal pain and itching. No unexpected treatment-related side effects were reported.
CONCLUSIONS
Advanced vulvar Paget's disease is a rare disorder and no standard treatment is available. In the sub-group of HER2 positive disease, weekly paclitaxel-trastuzumab appears to be active and safe, and may be considered a therapeutic option in these patients.

Identifiants

pubmed: 32998859
pii: ijgc-2020-001771
doi: 10.1136/ijgc-2020-001771
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
ERBB2 protein, human EC 2.7.10.1
Receptor, ErbB-2 EC 2.7.10.1
Trastuzumab P188ANX8CK
Paclitaxel P88XT4IS4D

Types de publication

Case Reports Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1672-1677

Informations de copyright

© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: FP reports grants from AstraZeneca, grants, personal fees and other from Roche, personal fees and other from Eli Lilly, personal fees from Amgen, personal fees from Ipsen, personal fees from MSD, personal fees from Takeda, grants and other from Eisai, other from Novartis and Pfizer, outside the submitted work; the other authors have nothing to disclose.

Auteurs

Michele Bartoletti (M)

Department of Medicine, University of Udine, Udine, Italy michele.bartoletti@cro.it.
Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Roberta Mazzeo (R)

Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Marco De Scordilli (M)

Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Anna Del Fabro (A)

Unit of Gynecological Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Centro di Riferimento Oncologico, Aviano, Italy.

Maria Grazia Vitale (MG)

Department of Medicine, University of Udine, Udine, Italy.
Department of Oncology, ASUFC Udine University Hospital, Udine, Italy.

Lucia Bortot (L)

Department of Medicine, University of Udine, Udine, Italy.
Department of Oncology, ASUFC Udine University Hospital, Udine, Italy.

Milena Sabrina Nicoloso (MS)

Unit of Molecular Oncology, Centro di Riferimento Oncologico, Aviano, Italy.

Serena Corsetti (S)

Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Marta Bonotto (M)

Department of Oncology, ASUFC Udine University Hospital, Udine, Italy.

Simona Scalone (S)

Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Giorgio Giorda (G)

Unit of Gynecological Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Centro di Riferimento Oncologico, Aviano, Italy.

Roberto Sorio (R)

Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

Claudia Andreetta (C)

Department of Oncology, ASUFC Udine University Hospital, Udine, Italy.

Maria Luisa Meacci (ML)

Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy.

Rocco De Vivo (R)

Department of Oncology, Ospedale San Bortolo, Azienda ULSS8 Berica, Vicenza, Italy.

Gianpiero Fasola (G)

Department of Oncology, ASUFC Udine University Hospital, Udine, Italy.

Francesco Sopracordevole (F)

Unit of Gynecological Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Centro di Riferimento Oncologico, Aviano, Italy.

Fabio Puglisi (F)

Department of Medicine, University of Udine, Udine, Italy.
Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy.

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