Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study

Namikawa, Kenjiro; Kiyohara, Yoshio; Takenouchi, Tatsuya; Uhara, Hisashi; Uchi, Hiroshi; Yoshikawa, Shusuke; Takatsuka, Sumiko; Koga, Hiroshi; Wada, Naoko; Minami, Hironobu; Hatsumichi, Masahiro; Asada, Suguru; Namba, Yoshinobu; Yamazaki, Naoya

doi:10.1016/j.ejca.2018.09.025

Cited by 53 publications

(74 citation statements)

References 32 publications

(36 reference statements)

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“…Another study (Reck et al, 2019) showed that first-line NIVO + IPI led to continuous early improvement in patients with advanced NSCLC and high TMB compared with chemotherapy. Japan's single-arm experiment (Namikawa et al, 2018) also highlighted the advantages of NIVO + IPI.…”

Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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Background: Combination therapy with immune checkpoint inhibitors (ICIs) has been applied in the clinic to achieve synergistic effects and to improve clinical efficacy. Compared with monotherapy, combination therapy has promising efficacy against various advanced cancers. To further verify the effectiveness of combination therapy, we conducted a meta-analysis of the efficacy and safety of nivolumab (NIVO) and NIVO plus ipilimumab (IPI) in advanced cancer. Methods: Electronic databases (PubMed, EMbase, and The Cochrane Library) were systematically searched for applicable studies published in English between January 1990 and June 2019. Relevant outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and grade 3-4 adverse events (AEs).

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Section: Discussionmentioning

confidence: 99%

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis

et al. 2020

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“…Among the 37 evaluable patients, the confirmed overall response rate was 24% in those with cutaneous melanoma and 25% in those with mucosal melanoma. A phase II trial of nivolumab and ipilimumab combination therapy was recently completed [ 50 •]. A total of 30 patients, including seven with acral and 12 with mucosal melanoma, were enrolled.…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapy and Immunotherapy for Melanoma in Japan

Namikawa¹,

Yamazaki²

2019

Curr. Treat. Options in Oncol.

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Opinion statementMelanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10–15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.

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“…To date, only a Japanese phase II clinical study has demonstrated the efficacy and safety of this treatment in Japanese patients. However, only 30 treatment‐naive patients were included 17 . Thus, the efficacy of nivolumab + ipilimumab combination therapy in Asian populations has not been demonstrated in clinical practice settings.…”

Section: Introductionmentioning

confidence: 99%

Real‐world efficacy and safety data of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma

Takahashi¹,

Namikawa²,

Ogata³

et al. 2020

The Journal of Dermatology

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The efficacy and safety of nivolumab + ipilimumab combination therapy were retrospectively examined in Japanese patients with unresectable advanced melanoma in clinical practice. Fifty‐seven patients with advanced melanoma received the nivolumab + ipilimumab combination therapy. The primary site was cutaneous, mucosal, uveal and unknown in 35, 16, two and four patients, respectively. The overall response rate was 26.3%, with complete response observed in two (3.5%) patients, partial response in 13 (22.8%), stable disease in 12 (21.1%) and progressive disease in 30 (52.6%). The response rate in the treatment‐naive and prior systemic therapy group was 40.7% and 13.3%, respectively. For those treated with a single immune checkpoint inhibitor followed by the nivolumab + ipilimumab combination therapy as second‐line therapy after disease progression, the response rate was 18.8%. Median progression‐free survival (PFS) and overall survival (OS) in all patients was 3.3 and 14 months, respectively. Median PFS in the treatment‐naive and prior systemic therapy groups was 13 and 2 months, respectively. Median OS was unreached in the treatment‐naive group and was 6.3 months in prior systemic therapy groups. There was no significant difference in PFS and OS for non‐acral, acral and mucosal melanoma. Adverse events occurred in 86% of patients; 56.1% were grade 3 or worse. The response rate in an actual clinical setting, including the prior systemic therapy group, was lower than that in the global study and the Japanese phase II study. However, in the treatment‐naive group, the rate was equivalent to that in the Japanese phase II study. PFS and OS in the treatment‐naive group were comparable with those in the global study and Japanese phase II study, suggesting that the treatment was effective. The proportion of grade 3 and 4 immune‐related adverse events was as high as that in the global study and Japanese phase II study.

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Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study

Cited by 53 publications

References 32 publications

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis

Comparative Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Advanced Cancer: A Systematic Review and Meta-Analysis

Targeted Therapy and Immunotherapy for Melanoma in Japan

Real‐world efficacy and safety data of nivolumab and ipilimumab combination therapy in Japanese patients with advanced melanoma

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