Real-world efficacy of anti-PD-1 antibody or combined anti-PD-1 plus anti-CTLA-4 antibodies, with or without radiotherapy, in advanced mucosal melanoma patients: A retrospective, multicenter study

Umeda, Yoshiyasu; Yoshikawa, Shusuke; Kiniwa, Yukiko; Maekawa, Takeo; Isei, Taiki; Matsushita, Satoru; Nomura, Motoo; Nakai, Yasuo; Fukushima, Satoshi; Saito, Shintaro; Takenouchi, Tatsuya; Tanaka, Ryo; Katô, Hiroshi; Otsuka, Atsushi; Matsuya, Taisuke; Baba, Norihisa; Nagase, Kotaro; Inozume, Takashi; Onuma, T; Kuwatsuka, Yutaka; Fujimoto, Noriki; Kaneko, Takahide; Onishi, Masazumi; Namikawa, Kenjiro; Yamazaki, Naoya; Nakamura, Yasuhiro

doi:10.1016/j.ejca.2021.08.034

Cited by 28 publications

(29 citation statements)

References 26 publications

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“…To improve the lower clinical efficacy of PD1 in MCM, additional treatment options with PD1 should be explored; however, very few studies have examined PD1 in combination with other treatment modalities, and they have used small sample sizes. Four studies have tested the efficacy of PD1 plus radiotherapy, including a study recently reported by our group, 22 , 23 , 24 , 25 two studies have tested PD1 plus a vascular endothelial growth factor receptor (VEGFR) inhibitor, 26 , 27 and four studies explored the efficacy of PD1 + CTLA4. 6 , 16 , 17 , 28 , 29 …”

Section: Discussionmentioning

confidence: 99%

“…Conversely, our previous retrospective analysis of 171 Japanese MCM patients (PD1: 115 patients, PD1 plus radiotherapy: 56 patients) focused on survival and reported no significant difference in ORR, PFS, and OS between the PD1 and PD1 plus radiotherapy groups (ORR, 26% versus 27%, P > 0.99; median PFS, 6.2 versus 6.8 months; P = 0.79; median OS, 19.2 versus 23.1 months; P = 0.70). 25 …”

Section: Discussionmentioning

confidence: 99%

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Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

Nakamura

Namikawa²,

Yoshikawa

et al. 2021

ESMO Open

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Background Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. Patients and methods We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. Results Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). Conclusions First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

Nakamura

Namikawa²,

Yoshikawa

et al. 2021

ESMO Open

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“…In a prospective clinical trial, 25 AM patients receiving a combination of RT and anti-PD-1 ICI had better outcomes at the irradiated and also the non-irradiated areas, that could be explained by the abscopal effect [ 25 ]. A further study reported that this combination showed significant benefit in 225 patients with advanced mucosal melanoma [ 26 ]. Another prospective study assessed a combination of RT and ICI therapy in AM patients who did not respond to anti-PD-1 monotherapy.…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Monotherapy in Advanced Melanoma—Real-World Data from a 77-Month-Long Retrospective Observational Study

et al. 2022

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Real-world evidence plays an important role in the assessment of efficacy and safety of novel therapies. The increasing use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has led to notably improved clinical outcomes, while they are also associated with immune-related adverse events (irAEs). The majority of the available data are based on clinical trials, where the investigated subjects often do not adequately represent the general patient population of the everyday practice. Although there is a niche of objective biomarkers for the future treatment response of ICIs, certain studies suggest that irAEs may be predictive. The aim of this study was to carry out a retrospective analysis of treatment data from patients with advanced melanoma, treated with a single anti-PD-1 agent (pembrolizumab or nivolumab) during a 77-month-long period. Treatment efficacy and occurrence of adverse events were analyzed to identify potential predictive markers. Primary and secondary endpoints were the overall survival (OS) and progression-free survival (PFS). In our cohort, we demonstrated that the occurrence of more than one irAE showed a correlation with response to PD-1 ICI therapy and improved the OS and PFS. Our study suggests, that the grade of toxicity of the irAE may affect the survival rate.

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“…Another strategy that has been explored to improve the low efficacy of ICIs in MM is ICI therapy in combination with radiotherapy. A multi-institutional retrospective study of 225 Japanese patients with MM evaluated anti-PD-1 monotherapy or anti-PD-1 + anti-CTLA-4 combination therapy with or without radiotherapy and found no survival benefit with RT in either ICI regimen ( 72 ). In the PD-1 cohort, ORR was 26% in PD1 alone versus 27% in PD1 + RT ( P > .99), and similarly, in the combination therapy cohort, ORR was 28% in PD1+CTLA4 vs 25% in PD1+CTLA4+RT ( P = .62) ( 72 ).…”

Section: Mucosal Melanomamentioning

confidence: 99%

Management of Acral and Mucosal Melanoma: Medical Oncology Perspective

Jung

Johnson

2022

The Oncologist

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Acral and mucosal melanomas (MM) are rare subtypes of melanoma that are biologically and clinically distinct from cutaneous melanoma. Despite the progress in the treatment of cutaneous melanomas with the development of targeted and immune therapies, the therapeutic options for these less common subtypes remain limited. Difficulties in early diagnosis, the aggressive nature of the disease, and the frequently occult sites of origin have also contributed to the poor prognosis associated with acral and MM, with substantially worse long-term prognosis. The rarity of these subtypes has posed significant barriers to better understanding their biological features and investigating novel therapies. Consequently, establishing standardized treatment guidelines has been a challenge. In this review, we provide a brief overview of the current knowledge regarding acral and MM, focusing on their epidemiology, genetic backgrounds, and unique clinical characteristics. Further discussion centers around the management of primary and advanced disease and the role of emerging targeted and immune therapies for these subtypes, specifically focusing on issues relevant to medical oncologists.

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Real-world efficacy of anti-PD-1 antibody or combined anti-PD-1 plus anti-CTLA-4 antibodies, with or without radiotherapy, in advanced mucosal melanoma patients: A retrospective, multicenter study

Cited by 28 publications

References 26 publications

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)

Anti-PD-1 Monotherapy in Advanced Melanoma—Real-World Data from a 77-Month-Long Retrospective Observational Study

Management of Acral and Mucosal Melanoma: Medical Oncology Perspective

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