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

Date 24 November 2018
Event ESMO Asia 2018 Congress
Session Poster display - Cocktail
Topics Melanoma
Immunotherapy
Presenter Yasuhiro Nakamura
Citation Annals of Oncology (2018) 29 (suppl_9): ix105-ix108. 10.1093/annonc/mdy439
Authors Y. Nakamura1, A. Takahashi2, K. Namikawa2, T. Takenouchi3, S. Kitano4, T. Fujita5, K. Kubota6, T. Yamanaka6, Y. Kawakami7, N. Yamazaki2
  • 1Department Of Skin Oncology/dermatology, Saitama Medical University International Medical Center, 350-1298 - Hidaka/JP
  • 2Department Of Dermatologic Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 3Department Of Dermatology, Niigata Cancer Center, 951-8566 - niigata/JP
  • 4Department Of Experimental Therapeutics, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5Division Of Cellular Signaling, Institute For Advanced Medical Research, Keio University School of Medicine, Tokyo/JP
  • 6Department Of Biostatistics And Epidemiology, Yokohama City University School of Medicine, Yokohama/JP
  • 7Division Of Cellular Signaling, Institute For Advanced Medical Research, Keio University School of Medicine, 160-8582 - Tokyo/JP

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.

Editorial acknowledgement

Clinical trial identification

Clinical trial information: UMIN000016608.

Legal entity responsible for the study

Public Health Research Foundation.

Funding

Ono Pharmaceutical Co., Ltd. Bristol-Myers Squibb.

Disclosure

Y. Nakamura: Speaker\'s fee: Bristol-Myers Squibb, Chugai Pharma, MSD, Maruho, Novartis, Ono, Taisho Toyama; Advisory board: MSD, Novartis; Honorarium: Bristol-Myers Squibb, Chugai Pharma, Kyowa-Kirin, Ono; Other: Bristol-Myers Squibb. K. Namikawa: Grant: Public Health Research Foundation. T. Takenouchi: Speaker\'s fee: Bristol-Myers Squibb, Chugai Pharma, MSD, Novartis, Ono. S. Kitano: Speaker\'s fee: AstraZeneca, Bristol-Myers Squibb, Celgene, Chugai Pharma, MSD, Maruho, Novartis, Ono, Pfizer, Sanofi, Taiho; Advisory board: MSD, Novartis, Bristol-Myers Squibb, Chugai Pharma, Ono; Research support: Astellas. T. Fujita, Y. Kawakami: Others: Public Health Research Foundation, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb. T. Yamanaka: Spaker\'s fee: Boehringer-Ingelheim, Chugai pharma, Taiho, Takeda; Grant: Taiho, Takeda. N. Yamazaki: Speaker\'s fee: Bristol-Myers Squibb, Chugai pharma, Merck Serono, MSD, Novartis Pharma, Ono, Takeda; Grant: Bristol-Myers Squibb, Chugai pharma, Merck Serono, MSD, Novartis Pharma, Ono. All other authors have declared no conflicts of interest.