Predictors of Treatment (Tx) Response and Progression in Braf V600E Metastatic Melanoma (Mm) Patients (Pts) with Brain Metastases (Bm) Receiving Vemurafenib (Vem) in a Real-World Setting

Abstract

ABSTRACT Aim: mM pts with BM are associated with poor prognosis. Selective BRAF inhibitors may have a significant role in the tx of BM but data are limited. This study investigates predictors of intracranial tx response and intracranial progression among BRAFV600E mM pts with BM receiving vem in a real-word setting. Methods: Demographic and clinical characteristics, disease progression status, and tx response data were collected from a chart review by a panel of US oncologists on 283 BRAFV600E mM pts with active BM receiving vem. Predictors of intracranial tx response (complete response [CR] or partial response [PR]) and intracranial disease progression while on vem were identified using logistic regression models. Results: At vem initiation, mean age was 57 years, 61% of pts were male, and 68% had ECOG 0-1. Median follow-up time after vem initiation was 5.7 months. 53% of pts discontinued vem tx and 7% of pts had a vem dose reduction. While on vem, 48% of pts achieved intracranial CR/PR and 46% of pts achieved extracranial CR/PR. Intracranial disease progression occurred in 28% of pts while on vem. Predictors of intracranial CR/PR were corticosteroid use while on vem and the use of vem as 1st line tx after BM diagnosis (Table). Pts with larger number and size of BM before vem were less likely to achieve intracranial CR/PR. Predictors of disease progression were progressive extracranial disease before vem, larger number and size of BM before vem, and extent of extracranial metastasic disease before vem. The use of local tx before vem was associated with a reduced risk of intracranial progression. Conclusions: In real-world practice, 48% pts achieved intracranial CR/PR when treated with vem. Predictors of tx response were lower size and number of BM, earlier use of vem, and corticosteroid use. Predictors of intracranial progression were larger size and number of BM, progressive extracranial disease before vem, extent of extracranial metastasic disease, and no local tx before vem. Prospective data on tx outcomes are warranted in this population with high unmet need. Odds ratio (95% CI) Predictors of Intracranial CR or PR Concomitant use of corticosteroids (ref: no use of corticosteroids) 3.7 (1.9; 7.0) Number of BM (ref: ≤ 3 BM) ≥ 4 BM 0.3 (0.1; 0.6) Diameter of the largest BM (ref: 5-10mm 0.2 (0.1; 0.7) ≥ 10mm 0.8 (0.3; 1.9) Vem as 1st line after BM diagnosis (ref: vem initiated later lines) 4.4 (1.4; 13.3) Predictors of Intracranial Progression Progressive extracranial metastatic disease before vem initiation (ref: stable/regressive) 4.8 (2.3; 10.1) Local treatment for BM (ref: no local treatments) 0.4 (0.2; 0.9) Number of BM (ref: ≤ 1 BM) 2-4 BM 1.5 (0.6; 3.6) ≥ 5 BM 8.2 (2.3; 28.8) Number of sites of extracranial metastases (ref: ≤ 1 site) 2 sites 3.7 (1.6; 8.8) ≥ 3 sites 1.9 (0.8; 4.8) Diameter of the largest BM (ref: 5-10mm 7.8 (2.1; 29.1) ≥ 10mm 3.3 (0.9; 11.7) Disclosure: G. Gibney: Geoffrey Thomas Gibney is an employee of the Moffitt Cancer Center and a consultant for Roche/Genentch; G. Gauthier: Genevieve Gauthier is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; C. Ayas: Charles Ayas is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; P. Galebach: Phil Galebach is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; E. Wu: Eric Wu is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply; Y.M. Yim: Yeun Mi Yim is an employee of Genentech Inc. and hold stock ownership of Roche; S.S. Abhyankar: Sarang S. Abhyankar is an employee of Genentech Inc. and hold stock ownership of Roche; C. Reyes: Carolina M. Reyes is an employee of Genentech Inc. and hold stock ownership of Roche; A. Guerin: Annie Guerin is an employee of Analysis Group, Inc., which has received consultancy fees from Genentech Inc. No other disclosures apply.