Real-life data for first-line combination immune- checkpoint inhibition and targeted therapy in patients with melanoma brain metastases

被引：13

作者：

Hilbers, Marie-Luise ^{[1
]}

Dimitriou, Florentia ^{[1
]}

Lau, Peter ^{[2
]}

Bhave, Prachi ^{[2
]}

McArthur, Grant A. ^{[2
]}

Zimmer, Lisa ^{[3
]}

Kudura, Ken ^{[4
]}

Gerard, Camille L. ^{[5
]}

Levesque, Mitchell P. ^{[1
]}

Michielin, Olivier ^{[5
]}

Dummer, Reinhard ^{[1
]}

Cheng, Phil F. ^{[1
]}

Mangana, Joanna ^{[1
]}

机构：

[1] Univ Hosp Zurich, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland

[2] Peter MacCallum Canc Ctr, Dept Med Oncol, Melbourne, Vic, Australia

[3] Univ Duisburg Essen, Univ Hosp Essen, Dept Dermatol, Essen, Germany

[4] Univ Hosp Zurich, Dept Nucl Med, Zurich, Switzerland

[5] Lausanne Univ Hosp CHUV, Precis Oncol Ctr, Dept Oncol, Lausanne, Switzerland

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 156卷

关键词：

Immunotherapy; Targeted therapy; Melanoma brain metastasis; Stereotactic radiosurgery; OPEN-LABEL; RADIATION; SURVIVAL; MULTICENTER; IMPACT;

D O I：

10.1016/j.ejca.2021.07.028

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune check-point inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM. Methods: MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS). Results: 53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6-(46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of pa-tients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2-7.6) and mOS 14.2 months (95% CI 8.99-26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI. Conclusion: Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice. 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

引用

页码：149 / 163

页数：15

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