Motoo Nomura1, Isao Oze2, Toshiki Masuishi3, Tomoya Yokota4, Hironaga Satake5, Shunichiro Iwasawa6, Ken Kato7, Masashi Andoh3. 1. Department of Medical Oncology, Kyoto University Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. excell@hkg.odn.ne.jp. 2. Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 3. Department of Clinical Oncology, Aichi Cancer Center Hospital, 54 Kawahara-choSakyo-ku, ShogoinKyoto, 606-8507, Japan. 4. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 5. Department of Medical Oncology, Kobe City Medical Center General Hospital, 54 Kawahara-choSakyo-ku, ShogoinKyoto, 606-8507, Japan. 6. Department of Respirology, Chiba University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan. 7. Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Abstract
BACKGROUND: Mucosal melanoma is a rare and aggressive malignancy with poorer response compared with cutaneous melanoma. Prospective trials of immune checkpoint inhibitors in unresectable or metastatic mucosal melanoma have not been reported. PURPOSE: This phase II trial assessed the efficacy and safety of nivolumab monotherapy for unresectable or metastatic mucosal melanoma. PATIENTS AND METHODS: Eligibility criteria were as follows: histological diagnosis of unresectable or metastatic mucosal melanoma; age ≥ 20 years; ECOG performance status 0 or 1; and with measurable lesions. Patients received nivolumab 2 mg/kg every 3 weeks. The primary endpoint was the response rate (RR) according to Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were overall survival, progression-free survival, disease control rate, and toxicity. RESULTS: Twenty patients were enrolled between December 2014 and July 2017. Two patients without measurable lesions and one patient with uveal melanoma were excluded from analysis of efficacy. The best overall RR was 23.5%. One patient achieved a complete response, three partial response, and five stable disease as their best response. The median progression-free survival was 1.4 months (95% CI 1.2-2.8). The median overall survival was 12.0 months (95% CI 3.5 to not reached). The 1-year overall survival was 50.0% (95% CI 25.9-70.0%). Treatment-related adverse events of grades 3 or 4 occurred in 15% (3/20) of the patients. Grade 3 adverse events were resolved by corticosteroid treatment. CONCLUSION: Although this trial met the primary endpoint, the RR was still unsatisfactory. Therefore, further treatment development is required.
BACKGROUND:Mucosal melanoma is a rare and aggressive malignancy with poorer response compared with cutaneous melanoma. Prospective trials of immune checkpoint inhibitors in unresectable or metastatic mucosal melanoma have not been reported. PURPOSE: This phase II trial assessed the efficacy and safety of nivolumab monotherapy for unresectable or metastatic mucosal melanoma. PATIENTS AND METHODS: Eligibility criteria were as follows: histological diagnosis of unresectable or metastatic mucosal melanoma; age ≥ 20 years; ECOG performance status 0 or 1; and with measurable lesions. Patients received nivolumab 2 mg/kg every 3 weeks. The primary endpoint was the response rate (RR) according to Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were overall survival, progression-free survival, disease control rate, and toxicity. RESULTS: Twenty patients were enrolled between December 2014 and July 2017. Two patients without measurable lesions and one patient with uveal melanoma were excluded from analysis of efficacy. The best overall RR was 23.5%. One patient achieved a complete response, three partial response, and five stable disease as their best response. The median progression-free survival was 1.4 months (95% CI 1.2-2.8). The median overall survival was 12.0 months (95% CI 3.5 to not reached). The 1-year overall survival was 50.0% (95% CI 25.9-70.0%). Treatment-related adverse events of grades 3 or 4 occurred in 15% (3/20) of the patients. Grade 3 adverse events were resolved by corticosteroid treatment. CONCLUSION: Although this trial met the primary endpoint, the RR was still unsatisfactory. Therefore, further treatment development is required.