Real-world outcomes of Asian patients with advanced BRAF-mutant melanoma treated with first-line BRAF/MEK inhibitors, anti-PD-1 monotherapy, or combination of nivolumab plus ipilimumab: A multicenter retrospective study in Japan (B-CHECK-RWD study).

Authors

Kenjiro Namikawa

Kenjiro Namikawa

Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan

Kenjiro Namikawa , Takamichi Ito , Shusuke Yoshikawa , Koji Yoshino , Yukiko Kiniwa , Tatsuya Takenouchi , Hiroshi Kato , Satoru Mizuhashi , Yosuke Yamamoto , Yasuhiro Fujisawa , Osamu Yamasaki , Yasuhiro Nakamura , Jun Asai , Takeo Maekawa , Shigeto Matsushita , Eiji Nakano , Kohei Oashi , Hisashi Uhara , Takuya Miyagawa , Naoya Yamazaki

Organizations

Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Dermatology, Shizuoka Cancer Center, Shizuoka, Japan, Department of Dermatologic Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan, Department of Dermatology, Shinshu University, Matsumoto, Japan, Department of Dermatology, Niigata Cancer Center Hospital, Niigata, Japan, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan, Department of Dermatology, Graduate School of Medicine, Chiba University, Chiba, Japan, Department of Dermatology, University of Tsukuba, Tsukuba, Japan, Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan, Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center, Saitama, Japan, Department of Dermatology, Kyoto Prefectural University of Medicine, Kyoto, Japan, Department of Dermatology, Jichi Medical University Hospital, Tochigi, Japan, Department of Dermato-Oncology/Dermatology, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan, Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan, Department of Dermatology, Saitama Cancer Center, Saitama, Japan, Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan, Department of Dermatology, University of Tokyo, Tokyo, Japan

Research Funding

Other Government Agency

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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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Melanoma/Skin Cancers

Track

Melanoma/Skin Cancers

Sub Track

Advanced/Metastatic Disease

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e21553)

DOI

10.1200/JCO.2022.40.16_suppl.e21553

Abstract #

e21553

Abstract Disclosures