Future oncology
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Bone is a common site for malignant involvement, either as a site of metastasis, especially in breast or prostate cancer, or as a defining characteristic of the disease, as in multiple myeloma. Bone disease is a major source of morbidity, and half of patients with bone involvement develop skeletal-related events such as pathological fractures or cord compression requiring surgery and/or radiation. ⋯ Osteoclast inhibition with bisphosphonates such as zoledronic acid and recently denosumab has been a significant improvement for bone disease. This review will focus on denosumab in the treatment of bone metastases and highlight the recent findings in multiple myeloma.
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Immune checkpoint inhibitors (ICIs) are a key component of treating advanced cancer patients, principally antibodies against CTLA-4 and PD-1 or PD-L1. Durvalumab (MEDI4736) is a selective, high-affinity, human IgG1 monoclonal antibody that blocks PD-L1, which binds to PD-1 and CD80, but not to PD-L2. ⋯ Impressive activity has been recently reported after chemoradiation in locally advanced patients; promising activity was observed with other ICI combinations, and potentially with other drugs including platinum-based chemotherapy. In contrast, early data reveal lower response rates in EGFR and ALK-positive patients.
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To assess the association between tumor response and health-related quality of life (HRQoL) in patients with metastatic Merkel cell carcinoma treated with the anti-PD-L1 avelumab. ⋯ In patients with metastatic Merkel cell carcinoma, nonprogression during treatment with avelumab correlated with gains in HRQoL.
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Randomized Controlled Trial
Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia.
Mutations in IDH2 genes (mIDH2) occur in approximately 12% of patients with acute myeloid leukemia. Enasidenib is an oral, small-molecule inhibitor of mIDH2 proteins. Enasidenib is shown to suppress the oncometabolite, 2-hydroxyglutarate, and promote differentiation of leukemic bone marrow blasts. ⋯ Median overall survival was 9.3 months. 2-hydroxyglutarate suppression did not predict response and mIDH2 clearance was possible, but not required for response. Patients with ≥6 co-mutations or NRAS co-mutations were less likely to attain a response. Enasidenib was safe and well tolerated with low rates of treatment-related adverse events. [Formula: see text].
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Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. Systemic chemotherapy is the primary treatment modality for the majority of patients. VEGF plays a key mitogen for MPM cells physiopathology. ⋯ Based on the results of the Phase III IFCT-0701 mesothelioma avastin cisplatin pemetrexed study, cisplatin-pemetrexed-bevacizumab is now the accepted standard in France. The National Comprehensive Cancer Network guidelines have also included this combination as an option for standard front-line therapy. This review summarized the efficacy and safety data of bevacizumab in the treatment of patients with MPM.