Real-world efficacy of chemotherapy in patients with advanced extramammary Paget's disease: A retrospective, multicenter study of 204 Japanese patients.
Authors: Miyashita Azusa , Fukushima Satoshi , Yoshino Koji , Kato Hiroshi , Yamazaki Naoya , Kawashima Shusuke , Yamamoto Yuki , Nakamura Yasuhiro , Kiniwa Yukiko , Ishizuki Shoichiro , Maekawa Takeo , Okada Etsuko , Fujimura Taku , Fujii Kazuyasu , Fujisawa Yasuhiro , Asai Jun , Otsuka Atsushi , Morinaga Jun , Matsushita Shigeto 
Published: June 2023

e21579 Background: Extramammary Paget's disease (EMPD) is a rare skin cancer that develops in the vulva, anus, and axilla. The incidence rate of EMPD is 0.13 per 100,000 population/year in Caucasians and 0.28 in Asians; thus, it is more frequent in Asians. Although distant metastases have been reported to occur in 10%-20% of all cases of EMPD, standard systemic chemotherapy for advanced EMPD has not been established worldwide. Retrospective studies conducted thus far have been insufficient due to their small sample sizes. Furthermore, there are no reports comparing the effectiveness of multiple treatments. To establish a standard treatment for advanced EMPD, prospective clinical trials are necessary, and we are planning a prospective clinical trial. As a pilot study, we investigated a large sample of patients with advanced EMPD and analyzed the efficacy of systemic chemotherapies. Methods: Patients with advanced EMPD who were treated in 16 Japanese institutions during 2011-2022 were evaluated. The efficacy of each treatment was estimated by determining the objective response rate (ORR) or progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier analysis. Multivariable analysis was performed to account for potential confounding factors, such as age, sex, and performance status (PS). A total of 204 patients were enrolled, of which 164 (80.4%) patients were treated as follows: Docetaxel hydrate (DOC), n = 108 (52.9%); tegafur/ gimeracil/ oteracil potassium (S-1)/DOC, n = 16 (7.8%); fluorouracil/cisplatin (FP), n = 26 (12.8%); fluorouracil/epirubicin/carboplatin/vincristine/mitomycin C (FECOM), n = 3 (1.5%); and other, n = 11 (5.4%). Forty (19.6%) patients received the best supportive care. Results: OS and PFS did not differ significantly among the DOC, S-1/DOC, FP, FECOM, and other groups (p = 0.176 and p = 0.568, respectively). The ORRs in the S-1/DOC, DOC, FP, and FECOM groups were 75.0%, 51.9 %, 38.5%, and 66.7%, respectively. The odds ratio for the ORR of the S-1/DOC group compared with the DOC group estimated by the logistic regression analysis with adjustment for age, sex, and PS was 2.72, (95% CI: 1.09-6.78, p = 0.032). S-1/DOC was the only treatment with a significantly higher ORR than that of DOC, which is the most frequently used treatment for advanced EMPD in Japan. Conclusions: Although there were no significant differences in PFS and OS between the multiple regimens, the S-1/DOC group showed significantly higher ORR compared with the DOC group. Because the high response rate to S-1/DOC greatly improves the quality of life of patients with advanced EMPD, S-1/DOC may be more beneficial than DOC and other regimens for the treatment of advanced EMPD. A phase II clinical trial of S-1/DOC is currently planned in Japan.