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Human epidermal growth factor receptor-2 (HER2) is a potential therapeutic target in extramammary Paget’s disease of the vulva
  1. Michele Bartoletti1,2,
  2. Roberta Mazzeo1,2,
  3. Marco De Scordilli1,2,
  4. Anna Del Fabro3,
  5. Maria Grazia Vitale1,4,
  6. Lucia Bortot1,4,
  7. Milena Sabrina Nicoloso5,
  8. Serena Corsetti2,
  9. Marta Bonotto4,
  10. Simona Scalone2,
  11. Giorgio Giorda3,
  12. Roberto Sorio2,
  13. Claudia Andreetta4,
  14. Maria Luisa Meacci6,
  15. Rocco De Vivo7,
  16. Gianpiero Fasola4,
  17. Francesco Sopracordevole3 and
  18. Fabio Puglisi1,2
  1. 1Department of Medicine, University of Udine, Udine, Italy
  2. 2Department of Medical Oncology, Unit of Medical Oncology & Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
  3. 3Unit of Gynecological Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Centro di Riferimento Oncologico, Aviano, Italy
  4. 4Department of Oncology, ASUFC Udine University Hospital, Udine, Italy
  5. 5Unit of Molecular Oncology, Centro di Riferimento Oncologico, Aviano, Italy
  6. 6Department of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy
  7. 7Department of Oncology, Ospedale San Bortolo, Azienda ULSS8 Berica, Vicenza, Italy
  1. Correspondence to Dr Michele Bartoletti, Department of Clinical Oncology and Prevention, Centro di Riferimento Oncologico, Aviano 33081, Italy; michele.bartoletti{at}


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/m2) followed by 3-weekly trastuzumab maintenance (6 mg/kg), are reported.

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.

  • paget disease
  • extramammary

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  • FS and FP contributed equally.

  • Contributors MB conceived the study. MB, RM, MDS, LB, and MGV wrote case reports. FS supervised the surgical aspects of the work. FP supervised the medical aspects of the work. All authors contributed to data interpretation, wrote, revised, and approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • 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.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data are included in the main article.