The University or college of Texas MD Anderson Malignancy Center is supported by the National Institutes of Health (grant P30 CA016672). Conflict of Interest Disclosures Jose Lutzky reports belonging to speakers bureaus for Array, Regeneron, and Novartis and to advisory boards for Novartis, Regeneron, Array, and SAR-100842 Bristol\Myers Squibb. with V600Cmutated melanoma.18, 23 However, the combination has not been formally studied in trials including patients with active brain metastases. In this analysis, we statement the results of a retrospective case series evaluating the antitumor activity of encorafenib plus binimetinib in patients with mutation, and had been treated with encorafenib plus binimetinib at 1 of the 3 participating study centers (Mount Sinai Comprehensive Malignancy Center, Miami Beach, Florida; Levine Malignancy Institute, Atrium Health, Charlotte, North Carolina; and The University or college of Texas MD Anderson Malignancy Center, Houston, Texas). Patients were excluded if they did not have measurable intracranial disease by magnetic resonance imaging (MRI) or if pre/post brain MRI imaging was not performed. Retrospective data collection included patients demographic characteristics, clinical history of melanoma and brain metastases (including the clinical features at diagnosis, course of the disease, treatment received, and outcomes), and encorafenib\binimetinib treatment exposure. Assessments included tumor responses to treatment (intracranial, extracranial, and global responses) evaluated with the altered Response Evaluation Criteria in Solid Tumors, version 1.1 (mRECIST1.1); the time to response; and the period of response. For the purposes of this study, refers to intra\axial lesions (ie, not intracranial lesions that were extra\axial). Security data were collected from a chart review and included adverse events, laboratory abnormalities, SAR-100842 and intolerance to encorafenib\binimetinib SAR-100842 therapy. Lactate dehydrogenase (LDH) levels were recorded at the start of treatment with encorafenib plus binimetinib and at the time of response or progression. For the response analysis, extracranial lesions (a minimum of 10?mm in diameter for measurable nonnodal lesions) were assessed according to the Response Evaluation Criteria in Sound Tumors, version 1.1. For the assessment of brain lesions, the Response Evaluation Criteria in Solid Tumors were altered to allow up to 5 intracranial target lesions, as explained previously.8, 12, 24 Imaging criteria were enhancing lesions on MRI brain axial T1 with contrast. Intracranial lesions were measured only with gadolinium\enhanced MRI and were considered measurable if the longest diameter was at least 5?mm. Global responses were assessed with the mRECIST1.1 criteria for brain lesions and systemic disease to encompass all index lesions in the brain and systemic compartments. Results for all those assessments and baseline data were summarized descriptively. The objective response rate was defined as the percentage of total and partial responses as evaluated with mRECIST1.1; KRT17 the clinical benefit rate was defined as the percentage of patients who experienced a total response, partial response, or stable disease for 4?months or longer (the 4\month threshold corresponds to the scanning frequency). All case reports were reviewed in accordance with SAR-100842 Helsinki principles and were approved by the institutional review boards at the individual institutions. Results Study Patients Information on patient disposition can be found in Physique ?Physique1.1. A total of 29 patients were screened, and 24 patients met the inclusion criteria for this analysis as of the data cutoff date of February 28, 2019. Of the 24 patients, 2 were treated at the Mount Sinai Comprehensive Malignancy Center, 7 were treated at the Levine Malignancy Institute, and 15 were treated at The University of Texas MD Anderson Malignancy Center. The reasons for screened patients to be excluded were a lack of measurable disease (3 patients) and a lack of scans (2 patients). Patients were initiated on the full doses of encorafenib (450?mg once daily) and binimetinib SAR-100842 (45?mg twice daily) with the exception of 4 patients who required dose reductions of one or both brokers. Open in a separate window Physique 1 Patient disposition. A summary of the patient demographics and clinical characteristics is shown in Table ?Table1.1. For the 24 patients included in this study, the.
The University or college of Texas MD Anderson Malignancy Center is supported by the National Institutes of Health (grant P30 CA016672)
