Lim, Sanghee

Abstract BACKGROUND Bevacizumab, an anti-VEGF monoclonal antibody, has become a mainstay in the management of malignant gliomas. Multiple bevacizumab biosimilars have been approved since initial FDA approval of the reference agent and have seen widespread use due to reduced cost. However, real-world data evaluating comparability between reference and biosimilar agents have remained limited. METHODS We performed a retrospective analysis of patients treated with reference bevacizumab (Avastin) versus those receiving bevacizumab-bvzr, a widely used biosimilar agent (Zirabev) for the management of malignant glioma at our institution between 2019 and 2022. RESULTS A total of 161 patients were included in our final analysis; 97 received reference drug (Avastin) while 64 received the biosimilar agent (Zirabev). Demographics and baseline clinical characteristics between the two groups were similar. We performed survival analysis with post-progression survival (PPS) to ensure against lead-time bias. PPS was similar between the Avastin (median PPS 496 days) and Zirabev (median PPS 513 days) groups on univariate analysis (p=0.7654). Similarly, on multivariate Cox regression, there were no differences in PPS when comparing Avastin and Zirabev (HR 1.0673, p=0.6986). MGMT promoter methylation (HR 0.5709, p=0.0238), age at cancer diagnosis (HR 1.0356, p=0.0009), total dose of bevacizumab received (HR 0.9975, p=0.0087) and treatment with anticoagulation (HR 1.8086, p=0.0372) were significantly associated with PPS. Rates of therapy-related adverse effects were also similar between those receiving the reference drug and biosimilar agent (OR 0.9043, p=0.7824). However, concomitant treatment with antiplatelet therapy (OR 3.1447, p=0.0150) or anticoagulant therapy (OR 4.9069, p=0.0010) were significantly associated with increased risk for adverse effects. CONCLUSIONS Bevacizumab-bvzr demonstrated similar clinical efficacy and safety profile compared to reference bevacizumab in our institutional cohort. Concomitant treatment with antiplatelet therapy (OR 3.1447, p=0.0150) or anticoagulation (OR 4.9069, p=0.0010) were significantly associated with increased risk for adverse effects.

Abstract BACKGROUND Hypercoagulability is a well-described paraneoplastic phenomenon associated with strokes in cancer patients, but whether driver mutations or antineoplastic treatments contribute in a significant way to recurrent stroke risk are not well understood. METHODS As part of a larger study focusing on lung cancer and stroke, we retrospectively identified 103 patients with tissue-confirmed adenocarcinoma and prior diagnosis of stroke treated at the Mayo Clinic between 2000-2022. We collected data regarding demographics, performance status, cerebrovascular risk factors, antithrombotic use, chemotherapy, radiation, and genetic testing data, which were assessed for impact on recurrent stroke risk. RESULTS 71.8% of patients had recurrent strokes (74/103). No class of chemotherapeutics was significantly associated with increased risk for recurrent strokes, including immune checkpoint inhibitors and thrombogenic chemotherapeutics (Gemcitabine, Cisplatin, Carboplatin, anti-VEGF therapies). 78 patients had genetic testing data available. Driver mutations in KRAS, EGFR, MET, and BRAF were not associated with increased risk for recurrent stroke. There was a signal towards increased risk for stroke recurrence in patients with ALK mutations (OR 2.647, p=0.4056). There was a trend towards increased risk for stroke recurrence in patients with advanced staging (Stage III/IV) at diagnosis (OR 2.125, p=0.09). Stroke recurrence risk was higher in patients treated with single antiplatelet agents compared to anticoagulation or dual antiplatelet therapy (OR 3.385, p=0.0061) though risk of hemorrhagic complications was similar (OR 1.559, p=0.3376). Patients with recurrent stroke had longer overall survival compared to those without (Median OS 43.2 months vs 26.3 months, Mantel-Haenszel HR 0.5202, p=0.0367). CONCLUSIONS In patients with lung adenocarcinoma who experienced ischemic stroke, prolonged survival and single antiplatelet therapy compared to dual antiplatelet therapy or anticoagulation were associated with increased recurrent stroke risk. ALK mutations and higher stage at initial diagnosis trended towards higher risk for stroke recurrence. Larger retrospective analyses are under way to confirm these findings.

Abstract Low-grade meningiomas with subtotal resection carry significantly shorter recurrence-free survival rates than those with gross total resection. We report the natural history of a case of low-grade meningioma after subtotal resection and review the literature. We aim to highlight known global health disparities in oncology treatment by describing a case of meningioma progression following subtotal resection. A 40-year-old Kenyan woman presented locally with headache, nausea, and vision loss over approximately a six month time period. A 5 cm olfactory groove meningioma was discovered, and she subsequently underwent subtotal resection that was likely limited due to hemorrhagic complications. Over the following two years, she developed progressive dizziness, nausea, gait instability, difficulty performing tasks, and visual loss prompting medical evaluation at our institution. Physical examination demonstrated blindness, bilateral proptosis with severe vertical gaze palsy, and prominent frontal bossing. MRI Brain revealed a 9 cm enhancing mass arising from the cribriform plate with elevation of an ununited overlying frontal craniotomy flap and apparent meningoceles extending through the presumed osteotomy bilaterally. She underwent successful resection with pathology demonstrating CNS WHO Grade 1 meningioma. Her postoperative neurologic exam showed subtle improvement, specifically in regards to orientation questions. In this patient, bone flap displacement from prior craniotomy allowed significant interval tumor growth while minimizing mass effect on brain parenchyma. This case highlights global health disparities in low-grade meningioma management related to appropriate healthcare access in underserved patients.