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

Abstract

BackgroundInvasive 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.MethodsFour 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.ResultsMedian 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.ConclusionsAdvanced 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.

Extramammary Paget’s Disease of the Vulva: Report of Two Cases

“…Although anti-HER-2 therapy has been tried in very few patients, it seems to reduce tumor size, and it is well tolerated by the patients. Very recently, trastuzumab-based treatments, mostly a paclitaxel–trastuzumab combination, have been described as leading to a complete or partial response in patients with invasive vulvar PD, thus strongly indicating the possibility that HER-2 inhibitors are suitable for adjuvant therapy [ 27 ].…”

Role of Chemotherapy in Vulvar Cancers: Time to Rethink Standard of Care?

“…An objective response was observed in all the patients, with a median duration of response of 10 months. Treatment was extremely well tolerated [71].…”

Extramammary Paget’s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments

“…As for molecular expression in EMPD lesions, multiple studies have demonstrated HER2 overexpression in EMPD lesions, which was associated with amplified ERBB2 [55,56]. These HER2-positive EMPD cases conferred a more aggressive biology [57]. In addition, Tanaka et al demonstrated that around 90% of patients with EMPD showed no difference in HER2 overexpression and ERBB2 gene amplification between primary lesions and lymph node (LN) metastasis, indicating that targeting therapies for HER2 may be effective for the treatment of both primary and metastatic lesions [58].…”

“…As described above, HER2 overexpression is frequently found in EMPD lesions, and HER2 may play crucial roles in the development and progression of EMPD in cases of HER2-positive tumors. Indeed, multiple cases of HER2-positive advanced EMPD have been reported that have shown the antitumor effects of anti-HER2 antibody, trastuzumab, monotherapy, or trastuzumab combined with other chemotherapies, such as paclitaxel or carboplatin [57,[143][144][145][146][147][148]. Most of these cases showed PFS of longer than 12 months, suggesting that anti-HER2 antibody is a promising therapy for advanced EMPD.…”