In patients harboring a glioma there was a very high incidence of symptomatic VTEs, particularly within 2 months of neurosurgery. The development of a VTE was associated with a 30% increase in the risk of death within 2 years. Further studies are needed to determine if risk stratification and the use of medical prophylaxis after neurosurgery improves outcomes.

520 Background: BRAF V600 mutations are associated with rare objective responses to the mutated BRAF inhibitor vemurafenib in patients with mCRC. Blockade of BRAFV600 by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. In murine models of BRAFV600 mCRC, the combination of irinotecan, cetuximab, and vemurafenib leads to greater anti-tumor activity, as suggested by a prior Phase 1B study. Methods: Patients (pts) with BRAFV600 mutated and extended RAS wild-type mCRC were randomized to irinotecan (180 mg/m2 IV every 14 days) and cetuximab (500 mg/m2 IV every 14 days) with or without vemurafenib (960 mg PO twice daily). Patients had received 1 or 2 prior regimens, with no prior anti-EGFR agents, although prior irinotecan was allowed. Crossover from the control arm to the experimental arm was allowed after documented progression. The primary endpoint was progression-free survival (PFS, investigator assessed), with 90% power to detect a HR of 0.5, with two-sided type 1 error of 5%. Results: 106 patients were enrolled (54 in the experimental arm) from 12/2014 to 4/2016, with ECOG PS ≤ 1. Median age of 62 years, 59% female, and prior irinotecan therapy in 39%. PFS was improved with the addition of vemurafenib (HR = 0.42, 95% confidence interval [CI] of 0.26 to 0.66, P < 0.001) with median PFS of 4.4 (95% CI: 3.6 – 5.7) months vs 2.0 (95% CI: 1.8 – 2.1). Response rate was 16% vs 4% (P = 0.09), with disease control rate of 67% vs 22% (P < 0.001). Grade 3/4 adverse events higher in the experimental arm included neutropenia (28% vs 7%), anemia (13% vs 0%), and nausea (15% vs 0%). There was no increase in skin toxicity or fatigue. No new safety signal was observed. Approximately 50% of patients in the control aim crossed over at the time of progression. Overall survival and efficacy at cross-over data remain immature. Conclusions: The addition of vemurafenib to the combination of cetuximab and irinotecan resulted in a prolongation of progression-free survival and a higher disease control rate, indicating that simultaneous EGFR and BRAF inhibition is effective in BRAFV600 mutated CRC. Clinical trial information: NCT02164916.

National Cancer Institute and Eli Lilly and Company.

Purpose This phase I study examined the toxicity and tolerability, of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. Experimental Design Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, zubrod performance status 0–2 and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5–36 mg/m2, and up to ten doses of docetaxel 75 mg/m2 every three weeks. Primary endpoints were safety, toxicity and a recommended phase II dose. Circulating arginine levels were measured prior to each cycle. Tumor response was measured as a secondary endpoint every six weeks on study. Results Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1st dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3–4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with ten patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including two patients with PSA response) were documented and seven patients had stable disease. Conclusions ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted and expansion cohorts are now accruing for both castrate resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m2.

PURPOSE To develop recommendations involving targeted therapies for patients with advanced gastroesophageal cancer. METHODS The American Society of Clinical Oncology convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS Eighteen randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS For human epidermal growth factor receptor 2 (HER2)–negative patients with gastric adenocarcinoma (AC) and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5, first-line therapy with nivolumab and chemotherapy (CT) is recommended. For HER2-negative patients with esophageal or gastroesophageal junction (GEJ) AC and PD-L1 CPS ≥ 5, first-line therapy with nivolumab and CT is recommended. First-line therapy with pembrolizumab and CT is recommended for HER2-negative patients with esophageal or GEJ AC and PD-L1 CPS ≥ 10. For patients with esophageal squamous cell carcinoma and PD-L1 tumor proportion score ≥ 1%, nivolumab plus CT, or nivolumab plus ipilimumab is recommended; for patients with esophageal squamous cell carcinoma and PD-L1 CPS ≥ 10, pembrolizumab plus CT is recommended. For patients with HER2-positive gastric or GEJ previously untreated, unresectable or metastatic AC, trastuzumab plus pembrolizumab is recommended, in combination with CT. For patients with advanced gastroesophageal or GEJ AC whose disease has progressed after first-line therapy, ramucirumab plus paclitaxel is recommended. For HER2-positive patients with gastric or GEJ AC who have progressed after first-line therapy, trastuzumab deruxtecan is recommended. In all cases, participation in a clinical trial is recommended as it is the panel's expectation that targeted treatment options for gastroesophageal cancer will continue to evolve. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .