The lancet oncology
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The lancet oncology · Dec 2016
Multicenter StudyOsimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study.
Osimertinib (AZD9291) is an oral, potent, irreversible EGFR tyrosine-kinase inhibitor selective for EGFR tyrosine-kinase inhibitor sensitising mutations, and the EGFR Thr790Met resistance mutation. We assessed the efficacy and safety of osimertinib in patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), who had progressed after previous therapy with an approved EGFR tyrosine-kinase inhibitor. ⋯ AstraZeneca.
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The lancet oncology · Dec 2016
ReviewReferral criteria for outpatient specialty palliative cancer care: an international consensus.
Although outpatient specialty palliative-care clinics improve outcomes, there is no consensus on who should be referred or the optimal timing for referral. In response to this issue, we did a Delphi study to develop consensus on a list of criteria for referral of patients with advanced cancer at secondary or tertiary care hospitals to outpatient palliative care. 60 international experts (26 from North America, 19 from Asia and Australia, and 11 from Europe) on palliative cancer care rated 39 needs-based criteria and 22 time-based criteria in three iterative rounds. Nearly all experts responded in each round. ⋯ Panellists reached consensus on 11 major criteria for referral: severe physical symptoms, severe emotional symptoms, request for hastened death, spiritual or existential crisis, assistance with decision making or care planning, patient request for referral, delirium, spinal cord compression, brain or leptomeningeal metastases, within 3 months of advanced cancer diagnosis for patients with median survival of 1 year or less, and progressive disease despite second-line therapy. Consensus was also reached on 36 minor criteria for specialist palliative-care referral. These criteria, if validated, could provide guidance for identification of patients suitable for outpatient specialty palliative care.
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The lancet oncology · Dec 2016
ReviewNeurological sequelae of cancer immunotherapies and targeted therapies.
Neurological complications of cancer and of anticancer treatments can be substantially disabling to patients, especially with classic chemotherapies. As a rare but important complication, targeted therapies might also result in similar unwanted effects, partly because inhibition of VEGF is a common downstream effect. ⋯ The prevalence of immune-related neurological adverse events might only be about 1%-a low prevalence compared with toxicities in other organs-but it constitutes new patterns of neurological toxic forms, which could result in considerable morbidity and fatal outcomes. Clinicians should be aware of treatment-associated neurotoxicity, and consider discontinuation of the drug with parallel supportive measures to help patients.
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The lancet oncology · Dec 2016
Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials.
Dabrafenib plus trametinib treatment provides significant benefits over BRAF-inhibitor monotherapy in patients with BRAFV600E-mutant or BRAFV600K-mutant advanced melanoma; however, in many patients the disease progresses, leading to death. With many treatment options available, understanding clinical factors that predict long-term response and survival for treatments is important for optimisation of patient management. We aimed to identify clinical factors associated with long-term response and survival using pooled data from randomised trials of dabrafenib plus trametinib in patients with metastatic BRAF-mutant melanoma. ⋯ Novartis.
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The lancet oncology · Dec 2016
Activity and safety of brigatinib in ALK-rearranged non-small-cell lung cancer and other malignancies: a single-arm, open-label, phase 1/2 trial.
Anaplastic lymphoma kinase (ALK) gene rearrangements are oncogenic drivers of non-small-cell lung cancer (NSCLC). Brigatinib (AP26113) is an investigational ALK inhibitor with potent preclinical activity against ALK mutants resistant to crizotinib and other ALK inhibitors. We aimed to assess brigatinib in patients with advanced malignancies, particularly ALK-rearranged NSCLC. ⋯ ARIAD Pharmaceuticals.