Interim analysis of prospective observational study on the efficacy of nivolumab for Japanese advanced melanoma patients (CREATIVE study)

Abstract

Background: Recent progress and better understanding of cancer immunology led to the development of anti-PD-1 antibody, which directed against the negative immunoregulatory cell surface receptor PD-1. Anti-PD-1 antibody nivolumab has been approved for advanced melanoma in Japan. Although there have been clinical trial reports on nivolumab treatment for advanced melanoma, the real-world data for nivolumab efficacy in Asian patient cohort is still lacking. The aim of this study is to obtain the real-world data for nivolumab efficacy in Japanese advanced melanoma patients. Methods: This prospective observational study was performed on unresectable or metastatic melanoma patients who were treated with nivolumab at a dose of 2mg/kg every 3 weeks (Q3W) or 3mg/kg every 2 weeks (Q2W). Primary endpoints are response rate (RR), and overall survival(OS). Biomarker analyses will also be planned at separate time points (before treatment, at 7, 13, 19, and 25 weeks). Results: In total, 125 patients from 22 institutions in Japan were enrolled between Dec. 2015 and Dec. 2017. Mucosal melanoma (25%) was the most frequent subtype in this study, followed by acral lentiginous melanoma (20%), nodular melanoma (16%), superficial spreading melanoma (13%), uveal melanoma (3%), and lentigo maligna melanoma (2%). Forty-eight patients (38%) were previously treated with any systemic therapies. We observed a CR in 1 (1%), PR in 21 (17%), SD in 34 (27%), and PD in 51 patients (49%) (objective RR: 18%). The difference of nivolumab dose (2mg/kg Q3W vs 3mg/kg Q2W) did not show significant difference in RR (objective RR, 17% vs 21%, P = 0.77; disease-control rate 41.1% vs 50%, P = 0.44, respectively). Use of nivolumab as a first-line treatment showed a tendency toward higher response than as a second-line treatment (objective RR, 20% vs 8%, P = 0.12). Conclusions: This interim analysis showed lower RR than that in the recent phase III randomized trials reported from western countries. The difference from western countries in proportion of subtypes of melanoma, having higher proportion of mucosal and acral melanoma, and the involvement of the second-line use of nivolumab will probably lead to lower RR to nivolumab in Japan.