Future oncology
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ABSTRACT Rearrangement of ALK gene has been identified as exerting a potent transforming effect as driver oncogene in patients with non-small-cell lung cancer (NSCLC). Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases. ⋯ Resistance mechanisms such as secondary gatekeeper mutations in ALK gene and activation of other oncogenes have been identified to confer acquired resistance to crizotinib. This article reviews the pharmacological properties of crizotinib, preclinical and clinical results that led to its approval in ALK-positive NSCLC and current directions of clinical research in overcoming crizotinib resistance.
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Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). ⋯ In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
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The PulMiCC trial is a randomized controlled trial testing the effect on survival of pulmonary metastasectomy in patients with colorectal cancer. In stage 1 of the trial patients with treated primary colorectal cancer metastatic to the lungs are invited to consent for protocol-based evaluation of their suitability for metastasectomy. ⋯ If there is uncertainty the patient is invited to consent to have the treatment arm assigned by randomization in stage 2 of PulMiCC. More than 300 patients have entered stage 1 and more than 70 are in stage 2.
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Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. ⋯ Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.
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Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, blocks PD-1 and can restore anticancer immune responses by abrogating PD-1 pathway-mediated T-cell inhibition. Nivolumab is approved in Japan and the USA for the treatment of patients with advanced melanoma. A Phase I trial reported overall objective response rates of 17, 32 and 29% in patients with advanced non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively, which included many heavily pretreated patients. 1-/2-year overall survival rates were 42%/24%, 63%/48% and 70%/50% for non-small-cell lung cancer, melanoma and renal cell carcinoma, respectively. ⋯ Nivolumab is associated with a manageable adverse event profile. Numerous clinical trials are investigating nivolumab alone or in combination with other therapies in multiple cancer settings. This article summarizes the development of nivolumab as of November 2014.