Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients

Sakaizawa, Kaori; Ashida, Atsuko; Uchiyama, Aya; Ito, Takamichi; Fujisawa, Yasuhiro; Ogata, Dai; Matsushita, Satoru; Fujii, Kazuyasu; Fukushima, Satoshi; Shibayama, Yuki; Hatta, Naohito; Takenouchi, Tatsuya; Uehara, Jiro; Okuyama, Ryuhei; Yamazaki, Naoya; Uhara, Hisashi

doi:10.1016/j.jdermsci.2015.07.012

Cited by 94 publications

(84 citation statements)

References 21 publications

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“…The percentage of patients with a BRAF mutation in this study was 25%, which was similar to that reported in 2 previous Japanese studies . The incidence of BRAF mutations is lower in Japanese patients than in Caucasian patients, although in the CheckMate 067 study, efficacy was confirmed regardless of BRAF status .…”

Section: Discussionsupporting

confidence: 88%

Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

Yamazaki¹,

Kiyohara

Uhara

et al. 2019

Cancer Science

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The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long‐term follow up of a single‐arm, open‐label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III / IV or recurrent melanoma. In addition, a post–hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate ( ORR ), and secondary endpoints included overall survival ( OS ), progression‐free survival ( PFS ), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment‐related adverse events ( TRAE ), including select immune‐related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [ CI ]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI : 34.7, 88.3) for superficial spreading, 33.3% (90% CI : 11.7, 65.3) for mucosal, and 28.6% (90% CI : 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3‐year OS rate was 43.5%, and the 3‐year PFS rate was 17.2%. A long‐term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long‐term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type.

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Section: Discussionsupporting

confidence: 88%

Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

Yamazaki¹,

Kiyohara

Uhara

et al. 2019

Cancer Science

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“…Mutations in BRAF have been noted in 50% of Caucasian patients, but in only 30–40% of Japanese patients . This difference is consistent with the fact that BRAF mutations are more frequently detected in superficial spreading melanoma (SSM), but are rarely detected in ALM …”

Section: Introductionsupporting

confidence: 87%

Japanese real‐world study of sequential nivolumab and ipilimumab treament in melanoma

Tsutsumida

Fukushima

Yokota

et al. 2019

The Journal of Dermatology

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To describe the treatment patterns of nivolumab and ipilimumab in Japan, a retrospective observational study was conducted in melanoma patients who received nivolumab and ipilimumab sequentially. Patients who received nivolumab and ipilimumab in combination were excluded from this study. Efficacy was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) in terms of the overall response rate (ORR), progression‐free survival (PFS), and disease control rate (DCR). Overall survival (OS) was also evaluated. Safety was assessed by the Common Terminology Criteria for Adverse Events (CTCAE). The treatment for all 68 patients enrolled involved switching from nivolumab to ipilimumab in 61 patients and switching from ipilimumab to nivolumab in seven patients. Switching occurred because of progressive disease in 55 patients and adverse events in eight patients. The median number of ipilimumab doses was three. Ipilimumab treatment achieved an ORR and DCR of 4.9% and 21.3%, respectively, and the median OS from start of ipilimumab was 7.0 months. During the study period, no new safety signals were noted. Independent factors which were indicative of poor prognosis for PFS were high neutrophil‐to‐lymphocyte ratio (NLR) and high C‐reactive protein (CRP) levels before ipilimumab treatment. An evaluation over a washout period indicated that no significant relationship existed with efficacy or safety. For the sequential administration of nivolumab and ipilimumab in Japanese melanoma patients, switch from nivolumab to ipilimumab was common, and the major reason for switching was progressive disease. The major prognostic factors for ipilimumab PFS after nivolumab were NLR and CRP before ipilimumab treatment.

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“…Indeed, Uhara and colleagues reported that among 171 Japanese melanoma patients, overall BRAF mutation frequency was only 30.4% due to the low frequency of the mutation in ALM and MCM . In their study, only 12.5% of nail bed, 8.9% of palm or sole, and none of the MCM patients had the BRAF mutation . Thus, nearly 70% of advanced melanoma that occur in the Japanese population would have no benefit from BRAF inhibitor and this is a great disadvantage when compared with Western countries that have more (>50%) BRAF mutations.…”

Section: Discussionmentioning

confidence: 92%

Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma

Yoshikawa²,

et al. 2019

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Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large‐scale Asian studies that include follow‐up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan‐Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease‐specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5‐year disease‐specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5‐year disease‐specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

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Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients

Cited by 94 publications

References 21 publications

Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

Japanese real‐world study of sequential nivolumab and ipilimumab treament in melanoma

Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma

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