Systemic therapy for Asian patients with advanced BRAF V600-mutant melanoma in a real-world setting: A multi-center retrospective study in Japan (B-CHECK-RWD study)

被引：19

作者：

Namikawa, Kenjiro ^{[1
]}

Ito, Takamichi ^{[2
]}

Yoshikawa, Shusuke ^{[3
]}

Yoshino, Koji ^{[4
,29
]}

Kiniwa, Yukiko ^{[5
]}

Ohe, Shuichi ^{[6
]}

Isei, Taiki ^{[6
]}

Takenouchi, Tatsuya ^{[7
]}

Kato, Hiroshi ^{[8
]}

Mizuhashi, Satoru ^{[9
]}

Fukushima, Satoshi ^{[9
]}

Yamamoto, Yosuke ^{[10
]}

Inozume, Takashi ^{[10
]}

Fujisawa, Yasuhiro ^{[11
,30
]}

Yamasaki, Osamu ^{[12
,31
]}

Nakamura, Yasuhiro ^{[13
]}

Asai, Jun ^{[14
]}

Maekawa, Takeo ^{[15
]}

Funakoshi, Takeru ^{[16
]}

Matsushita, Shigeto ^{[17
]}

Nakano, Eiji ^{[1
,18
]}

Oashi, Kohei ^{[19
]}

Kato, Junji ^{[20
]}

Uhara, Hisashi ^{[20
]}

Miyagawa, Takuya ^{[21
]}

Uchi, Hiroshi ^{[22
]}

Hatta, Naohito ^{[23
]}

Tsutsui, Keita ^{[24
]}

Maeda, Taku ^{[25
]}

Matsuya, Taisuke ^{[26
]}

Yanagisawa, Hiroto ^{[27
]}

Muto, Ikko ^{[28
]}

Okumura, Mao ^{[1
]}

Ogata, Dai ^{[1
]}

Yamazaki, Naoya ^{[1
]}

机构：

[1] Natl Canc Ctr, Dept Dermatol Oncol, 5-1-1 Tsukiji,Chuo Ku, Tokyo, 1040045, Japan

[2] Kyushu Univ, Grad Sch Med Sci, Dept Dermatol, Fukuoka, Japan

[3] Shizuoka Canc Ctr, Dept Dermatol, Shizuoka, Japan

[4] Tokyo Metropolitan Canc & Infect Dis Ctr Komagome, Dept Dermatol Oncol, Tokyo, Japan

[5] Shinshu Univ, Dept Dermatol, Matsumoto, Japan

[6] Osaka Int Canc Inst, Dept Dermatol Oncol, Osaka, Japan

[7] Niigata Canc Ctr Hosp, Dept Dermatol, Niigata, Japan

[8] Nagoya City Univ, Dept Geriatr & Environm Dermatol, Nagoya, Japan

[9] Kumamoto Univ, Dept Dermatol & Plast Surg, Kumamoto, Japan

[10] Chiba Univ, Dept Dermatol, Chiba, Japan

[11] Univ Tsukuba, Dept Dermatol, Tsukuba, Japan

[12] Okayama Univ, Dept Dermatol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[13] Saitama Med Univ, Dept Skin Oncol Dermatol, Int Med Ctr, Saitama, Japan

[14] Kyoto Prefectural Univ Med, Dept Dermatol, Kyoto, Japan

[15] Jichi Med Univ Hosp, Dept Dermatol, Shimotsuke, Tochigi, Japan

[16] Keio Univ, Dept Dermatol, Tokyo, Japan

[17] Natl Hosp Org Kagoshima Med Ctr, Dept Dermatooncol Dermatol, Kagoshima, Japan

[18] Kobe Univ, Dept Dermatol, Kobe, Japan

[19] Saitama Canc Ctr, Dept Dermatol, Saitama, Japan

[20] Sapporo Med Univ, Dept Dermatol, Sapporo, Japan

[21] Univ Tokyo, Dept Dermatol, Tokyo, Japan

[22] Natl Hosp Org Kyushu Canc Ctr, Dept Dermatooncol, Fukuoka, Japan

[23] Toyama Prefectural Cent Hosp, Dept Dermatol, Toyama, Japan

[24] Fukuoka Univ, Dept Dermatol, Fukuoka, Japan

[25] Hokkaido Univ, Dept Plast & Reconstruct Surg, Sapporo, Japan

[26] Asahikawa Med Univ, Dept Dermatol, Asahikawa, Japan

[27] Saitama Med Univ, Dept Dermatol, Saitama, Japan

[28] Kurume Univ, Dept Dermatol, Kurume, Japan

[29] Japanese Fdn Canc Res, Dept Dermatol Oncol, Canc Inst Hosp, Tokyo, Japan

[30] Ehime Univ, Dept Dermatol, Matsuyama, Ehime, Japan

[31] Shimane Univ, Dept Dermatol, Fac Med, Matsue, Shimane, Japan

来源：

CANCER MEDICINE | 2023年 / 12卷 / 17期

关键词：

Asian; BRAF; immune-checkpoint inhibitor; melanoma; targeted therapy; METASTATIC MELANOMA; EFFICACY; SAFETY; COMBINATION; BLOCKADE; CANCER; IMMUNOTHERAPY; DABRAFENIB; TRAMETINIB; NIVOLUMAB;

D O I：

10.1002/cam4.6438

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different.Methods: We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan.Results: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression-free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti-PD-1 and PD-1/CTLA-4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity-score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD-1/CTLA-4 (HRs for PD-1/CTLA-4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second-line treatment, BRAF/MEKi followed by PD-1/CTLA-4 showed poor survival outcomes.Conclusions: The superiority of PD-1/CTLA-4 over BRAF/MEKi appears modest in Asian patients. First-line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients.

引用

页码：17967 / 17980

页数：14

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