Phase II clinical trial of docetaxel and trastuzumab for HER2-positive advanced extramammary Paget's disease
Ikuko Hirai1, Keiji Tanese1, Yoshio Nakamura1
1Department of Dermatology, Keio University School of Medicine, Tokyo 160-8582Japan.
Background:
No consensus has been reached regarding the optimal chemotherapy for metastatic extramammary Paget's disease (EMPD), a rare cutaneous adenocarcinoma, because of the lack of solid evidence from prospective trials. However, the immunohistochemical profile of EMPD reportedly resembles that of breast cancer, particularly in terms of human epidermal growth factor receptor 2 (HER2) expression, suggesting that HER2 is a promising therapeutic target for advanced HER2-positive EMPD.
Methods:
In this phase II single-arm trial, 13 Japanese patients received intravenous trastuzumab (loading dose of 8 mg/kg and maintenance dose of 6 mg/kg) and docetaxel (75 mg/m2) every 3 weeks for up to 2 years. The docetaxel dose was reduced or discontinued according to its toxicity. The primary trial endpoints were objective response rate (ORR) after 3 cycles of treatment and safety throughout the study period.
Results:
All 13 patients completed 3 cycles of combination therapy. The median follow-up was 27.9 months. The ORR was 76.9% (n = 10/13; 90% CI, 50.5-93.4). Frequently observed adverse events were neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all of which were well tolerated.
Conclusion:
The combination of docetaxel and trastuzumab demonstrated a favorable clinical effect and acceptable tolerability, which makes it a good treatment option for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).
Insights
This study shows that combining docetaxel and trastuzumab is an effective treatment for metastatic extramammary Paget's disease (EMPD). The combination therapy demonstrated a high objective response rate and was well-tolerated by patients with HER2-positive EMPD.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Metastatic extramammary Paget's disease (EMPD) lacks a consensus optimal chemotherapy regimen due to limited prospective trial data.
- EMPD's immunohistochemical profile, similar to breast cancer, highlights human epidermal growth factor receptor 2 (HER2) as a potential therapeutic target.
- Targeting HER2 is a promising strategy for advanced HER2-positive EMPD.
Purpose of the Study:
- To evaluate the efficacy and safety of combination chemotherapy for metastatic extramammary Paget's disease.
- To assess the objective response rate (ORR) and tolerability of docetaxel plus trastuzumab in HER2-positive EMPD patients.
Main Methods:
- A phase II, single-arm trial involving 13 Japanese patients with metastatic EMPD.
- Patients received intravenous trastuzumab and docetaxel every 3 weeks for up to 2 years.
- Dose adjustments for docetaxel were based on toxicity; primary endpoints were ORR after 3 cycles and overall safety.
Main Results:
- All 13 patients completed 3 cycles of combination therapy, with a median follow-up of 27.9 months.
- An objective response rate (ORR) of 76.9% (10/13 patients) was observed.
- Common adverse events included neutropenia (100%), hypoalbuminemia (84.6%), and mucocutaneous infection (84.6%), all manageable.
Conclusions:
- The combination of docetaxel and trastuzumab demonstrated significant clinical efficacy in treating HER2-positive metastatic EMPD.
- This combination therapy exhibits acceptable tolerability, establishing it as a viable treatment option.
- The study provides evidence supporting docetaxel plus trastuzumab for HER2-positive metastatic EMPD (ClinicalTrials.gov Identifier: UMIN000021311, jRCTs031180073).
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