Future oncology
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The incidence of melanoma continues to rise worldwide. Prior to 2010, there had been no progress in the treatment of advanced melanoma in living memory. ⋯ The clinical benefit of nivolumab as a single agent is well established, with response rates of ≥40%, durable responses and a favorable tolerability profile. The combination of nivolumab and ipilimumab has also become a standard of care and the role of nivolumab in the adjuvant setting for high-risk patients has been recently confirmed.
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Review
The current landscape of early drug development for patients with sarcoma in the immunotherapy era.
Immunotherapy has changed the treatment paradigm of melanoma and other malignancies. Recently, trials of checkpoint inhibition in sarcomas have been far from outstanding, although specific sarcoma subtypes appear to benefit from these novel therapies. ⋯ Currently, numerous clinical trials are exploring different immunotherapies in the sarcomas. Herein, we describe some of the preclinical and clinical data that have laid the groundwork for the use of immunotherapies in sarcomas, as well as the current and future studies that could make immunotherapy a therapeutic option for patients with sarcoma.
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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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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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Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer that occurs in the elderly, is associated with UV radiation and immunosuppression. Initial treatment consists of wide excision with adjuvant radiation. ⋯ A study of an anti-PD-L1 antibody, avelumab, in chemotherapy-refractory MCC demonstrated a response rate of 31.8% resulting in FDA approval in March 2017 and EMA in September 2017. This review will discuss the disease, role of avelumab and other emerging treatment strategies for MCC.