The gut microbiome has attracted significant attention as a disease modifier of melanoma. A recent study has shown that the microbial diversity in the skin microbiome was lower in patients with melanoma than in patients with nevi. 1 However, no study has reported the association, if any, between the skin microbiome and clinical findings in melanoma. Therefore, we investigated the clinical significance of the skin microbiome in patients with acral melanoma. This study was performed in accordance with the Declaration of Helsinki principles and was approved by the institutional review board of Kumamoto University Hospital. Written informed consent was obtained from all patients included in this study. We retrospectively investigated 27 patients with acral melanoma who presented to Kumamoto University Hospital between April 2013 and April 2020. Cancer staging was performed based on the 8th edition of the American Joint Committee on Cancer/Union for International Cancer Control melanoma staging system. Immunohistochemistry was performed using a primary antibody against interleukin (IL)-17 (Abcam, Cambridge, UK) as described previously.

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BackgroundAnti‐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.MethodsWe 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.ResultsWe 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.ConclusionsThe 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.

e21553 Background: The systemic treatment for advanced BRAF-mutant melanoma includes BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (aPD1), and the combination of nivolumab plus ipilimumab (NIVO/IPI). Several studies have demonstrated favorable survival benefits for those treated with immunotherapy upfront. Most of these studies, however, were conducted among Caucasian-dominant cohorts; evidence for Asian patients is limited. Therefore, our objective was to assess the efficacy of first-line therapies for Asian patients in a real-world setting. Methods: We retrospectively collected the clinical data of Asian patients with advanced BRAF-mutant melanoma treated with first-line BRAF/MEKi, aPD1, or NIVO/IPI from 26 institutions in Japan. Clinical outcomes were determined by assessing the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) by first-line therapies. Kaplan‐Meier curves and log‐rank tests, as well as multivariable Cox proportional hazard models were used to estimate survival probabilities. Results: We identified 316 Asian patients treated with first-line BRAF/MEKi (n = 224), aPD1 (n = 59), or NIVO/IPI (n = 33) between 2016 and 2021. At baseline, the median age of the patients in each treatment arm was 63, 62, and 54, respectively (p = 0.053). The ORR in the first-line therapy was 69%, 29%, and 27%, respectively (p < 0.001). With a median follow-up of 18.9 months, the median PFS was 16.2, 5.6, and 6.4 months (p = 0.001); and the median OS was 36.9, 37.9 months, and not reached (p = 0.386), respectively. In a multivariable analysis, the predictive factors of short PFS were first-line therapy with aPD1 (HR, 2.44; 95%CI, 1.70-3.50, p < 0.001) or NIVO/IPI (1.73; 1.06–2.83, p = 0.029), BRAF V600K (p = 0.031), ECOG PS ≥2 (p = 0.011), elevated lactate dehydrogenase (LDH) levels (p = 0.001), and M1a/M1c/M1d stages (p = 0.036/ < 0.001/ < 0.001, respectively). Predictive factors of short OS were BRAF V600K (p = 0.042), ECOG PS ≥2 (p = 0.001), elevated LDH levels (p < 0.001), and M1c/M1d stages (both p < 0.001). The OS did not differ significantly by first-line therapies between BRAF/MEKi, aPD1 (1.52; 0.98–2.34, p = 0.061), and NIVO/IPI (0.63; 0.31–1.27, p = 0.194). Conclusions: Although upfront NIVO/IPI showed the longest OS numerically, its superiority over BRAF/MEKi in Asian patients seems to be modest compared with Caucasian patients. Because upfront BRAF/MEKi showed an OS that was comparable with that of aPD1, BRAF/MEKi remains an active first-line therapy option, especially for those who are not amenable to take the high risk of immune-related toxicities.

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