First line immunotherapy extends brain metastasis free survival, improves overall survival, and reduces the incidence of brain metastasis in patients with advanced melanoma

被引：5

作者：

Wang, Xuechen ^{[1
,2
]}

Haaland, Benjamin ^{[1
,2
]}

Hu-Lieskovan, Siwen ^{[1
,3
]}

Colman, Howard ^{[1
,4
]}

Holmen, Sheri L. ^{[1
,5
,6
]}

机构：

[1] Univ Utah, Hlth Sci Ctr, Huntsman Canc Inst, Salt Lake City, UT USA

[2] Univ Utah, Dept Populat Hlth Sci, Salt Lake City, UT USA

[3] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA

[4] Univ Utah, Hlth Sci Ctr, Dept Neurosurg, Salt Lake City, UT USA

[5] Univ Utah, Dept Surg, Hlth Sci Ctr, 2000 Circle Hope, Salt Lake City, UT 84112 USA

[6] Univ Utah, Hlth Sci Ctr, Dept Oncol Sci, Salt Lake City, UT USA

来源：

CANCER REPORTS | 2021年 / 4卷 / 06期

关键词：

first line therapy; immunology; melanoma; metastasis; target therapy; DABRAFENIB PLUS TRAMETINIB; STAGE-III; MEK INHIBITION; DOUBLE-BLIND; OPEN-LABEL; IPILIMUMAB; NIVOLUMAB; MULTICENTER; THERAPY; PLACEBO;

D O I：

10.1002/cnr2.1419

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Recent advances in targeted therapy and immunotherapy have improved the prognosis of melanoma patients but brain metastasis remains a major challenge. Currently, it is unclear how existing therapies can be best used to prevent or treat brain metastasis in melanoma patients. Aims We aimed to assess brain metastasis free survival (BMFS), overall survival (OS), incidence of brain metastases, and sequencing strategies of immunotherapy and targeted therapy in patients with BRAF-mutated advanced melanoma. Methods and results We retrospectively analyzed 683 patients with BRAF-mutated advanced melanoma treated with first line (1L) immunotherapy (N = 266) or targeted therapy (N = 417). The primary outcome was BMFS. Secondary outcomes included OS of all patients and incidence of brain metastases in patients without documented brain metastases prior to 1L therapy. The median BMFS was 13.7 months [95% confidence interval (CI): 12.4-16.0] among all patients. The median BMFS for patients receiving 1L immunotherapy was 41.9 months [95% CI: 22.8-not reached (NR)] and targeted therapy was 11.0 months (95% CI: 8.8-12.5). Median OS results were qualitatively similar to BMFS results. The cumulative incidence of brain metastases for patients receiving 1L targeted therapy was higher than for patients receiving 1L immunotherapy (P < .001). Patients receiving 1L anti-CTLA4 plus anti-PD1 combination immunotherapy only or followed by second line (2L) targeted therapy had better BMFS (HR 0.40, 95% CI: 0.24-0.67, P = .001), improved OS (HR 0.49, 95% CI: 0.30-0.81, P = .005), and reduced incidence of brain metastases (HR 0.47, 95% CI: 0.24-0.67, P = .047) than patients receiving 1L combination BRAF and MEK targeted therapy followed by 2L immunotherapy. Conclusion Patients with advanced BRAF mutant melanoma treated with 1L immunotherapy have significantly longer BMFS and OS, and reduced incidence of brain metastases, compared with those treated with 1L targeted therapy. Further studies evaluating the ability of immunotherapy and targeted therapy to improve OS and prevent brain metastases are warranted

引用

页数：10