Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma.

PURPOSE: Although fewer than 5% of high-grade gliomas (HGG) are BRAF-V600E mutated, these tumors are notable as BRAF-targeted therapy shows efficacy for some populations. The purpose of this study was to evaluate response to the combination of encorafenib with binimetinib in adults with recurrent BRAF-V600-mutated HGG. PATIENTS AND METHODS: In this phase 2, open-label, Adult Brain Tumor Consortium (ABTC) trial (NCT03973918), encorafenib and binimetinib were administered at their FDA-approved doses continuously in 28-day cycles. Eligible patients were required to have HGG or glioblastoma with a BRAF-V600E alteration that was recurrent following at least one line of therapy, including radiotherapy. RESULTS: Five patients enrolled between January 2020 and administrative termination in November 2021 (due to closure of the ABTC). Enrolled patients received treatment for 2 to 40 months; currently one patient remains on treatment. Centrally determined radiographic response rate was 60%, with one complete response and two partial responses. Methylation profiling revealed that all tumors cluster most closely with anaplastic pleomorphic xanthoastrocytoma (PXA). Transcriptional profile for MAPK-response signature was similar across all tumors at baseline and did not correlate with response in this small population. Circulating tumor DNA measured in plasma samples before treatment, during response, and upon progression showed feasibility of detection for the BRAF-V600E alteration. No new safety signal was detected. CONCLUSIONS: Encorafenib and binimetinib exhibit positive tumor responses in patients with recurrent BRAF-V600E mutant HGG in this small series, warranting therapeutic consideration. Although toxicity remains a concern for BRAF-targeted therapies, no new safety signal was observed in these patients.

Risk factors and prognosis of ovarian vein thrombosis.

: Ovarian vein thrombosis (OVT) remains poorly understood with no consensus regarding its importance or treatment. In this retrospective study, we investigated the clinical features, risk factors, treatment patterns, and prognosis of patients with OVT, including venous thromboembolism (VTE) recurrences. Adult patients who presented to our medical center with an identifiable diagnosis of OVT over a 10-year period were included in this retrospective observational study. Individual patient charts were reviewed to collect baseline and outcomes data. We identified 223 women with OVT. Median follow-up was 857 days. Only 36.6% presented with abdominal pain and 61.4% reported a history of gynecologic surgery. Overall, right or left OVT incidence was similar (44.6 and 41.4%, respectively) but peripartum patients were more likely to have right OVT (60.0%, P = 0.03). VTE recurred in 22 (9.9%) women, all of which were remote from the OVT and there were no recurrences in peripartum patients. Mean (±â€ŠSD) time to recurrence was 409 (±â€Š421) days. Only 7.6% of OVT patients were anticoagulated for OVT; these women had a 38% reduction in VTE recurrence but because of low numbers, this was not statistically significant. VTE recurrence after OVT was associated with greater mortality in all patients, including patients with cancer. OVT is associated with an increased rate of non-OVT recurrence. Peripartum OVT patients appear to constitute a different patient population as they were younger, exhibited different risk factors, and had no increased incidence of recurrence. Although only a minority of patients with OVT was anticoagulated, this group had a reduction in VTE recurrence. A prospective study is needed to determine the utility of anticoagulation for women with OVT.