The lancet oncology
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Cancers can evade the host immune system by inducing upregulation of immune inhibitory signals. Anti-programmed cell death-1 (PD-1) monoclonal antibodies block these inhibitory signals allowing the host to mount an immune response against malignant cells. ⋯ However, early clinical trials using PD-1 inhibitors have shown significant clinical activity in various subtypes of relapsed lymphoma. In this Review, we assess the scientific literature on the role of the PD-1 pathway in lymphoma, the relevant clinical data for PD-1 inhibition, and future strategies for this next generation of anticancer agents.
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The lancet oncology · May 2015
Randomized Controlled TrialNilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial.
Nilotinib inhibits the tyrosine kinase activity of ABL1/BCR-ABL1 and KIT, platelet-derived growth factor receptors (PDGFRs), and the discoidin domain receptor. Gain-of-function mutations in KIT or PDGFRα are key drivers in most gastrointestinal stromal tumours (GISTs). This trial was designed to test the efficacy and safety of nilotinib versus imatinib as first-line therapy for patients with advanced GISTs. ⋯ Novartis Pharmaceuticals.
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The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the major papillomavirus virion protein) virus-like particle (VLP) vaccines are regarded as safe, effective, and well established prophylactic vaccines. However, they have some inherent limitations, including a fairly high production and delivery cost, virus-type restricted protection, and no reported therapeutic activity, which might be addressed with the development of alternative dosing schedules and vaccine products. A change from a three-dose to a two-dose protocol for the licensed HPV vaccines, especially in younger adolescents (aged 9-13 years), is underway in several countries and is likely to become the future norm. ⋯ These two approaches would add an HPV component to existing live attenuated vaccines for measles and typhoid fever. Prophylactic vaccines that are based on induction of broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are also being developed both as simple monomeric fusion proteins and as virus-like display vaccines. The strong interest in developing the next generation of vaccines, particularly by manufacturers in middle-to-high income countries, increases the likelihood that vaccine production will become decentralised with the hope that effective HPV vaccines will be made increasingly available in low-resource settings where they are most needed.
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The lancet oncology · May 2015
Randomized Controlled TrialPazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial.
Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. ⋯ National Cancer Institute of Napoli and GlaxoSmithKline.
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The lancet oncology · May 2015
Randomized Controlled TrialAfatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.
Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. ⋯ Boehringer Ingelheim.