The lancet oncology
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The lancet oncology · Aug 2019
Multicenter StudyRamucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial.
Pre-clinical and clinical evidence suggests that simultaneous blockade of VEGF receptor-2 (VEGFR-2) and PD-1 or PD-L1 enhances antigen-specific T-cell migration, antitumour activity, and has favourable toxicity. In this study, we aimed to assess the safety and preliminary antitumour activity of ramucirumab (an IgG1 VEGFR-2 antagonist) combined with pembrolizumab (an IgG4 PD-1 antagonist) in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma, non-small-cell lung cancer, or urothelial carcinoma. ⋯ Eli Lilly and Company, and Merck and Co.
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The lancet oncology · Aug 2019
Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate comprised of trastuzumab covalently bound to a linker drug containing duocarmycin. Preclinical studies showed promising antitumour activity in various models. In this first-in-human study, we assessed the safety and activity of trastuzumab duocarmazine in patients with advanced solid tumours. ⋯ Synthon Biopharmaceuticals.
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The lancet oncology · Aug 2019
ReviewEnhancing CAR T-cell therapy through cellular imaging and radiotherapy.
Chimeric antigen receptor (CAR) T-cell therapy is one of the most remarkable advances in cancer therapy in the last several decades. More than 300 adoptive T-cell therapy trials are ongoing, which is a testament to the early success and hope engendered by this line of investigation. ⋯ In this Series paper, we discuss the short-term strategies to improve CAR T-cell therapy responses, particularly for solid tumours, by combining CAR T-cell therapy with radiotherapy through the use of careful monitoring and non-invasive imaging. Through the use of imaging, we can gain greater mechanistic insights into the cascade of events that must unfold to enable tumour eradication by CAR T-cell therapy.
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Evidence to date shows that immune checkpoint inhibitors have little benefit in most patients with head and neck squamous cell carcinoma (HNSCC). Intense interest is focused on identifying and developing rational combinations of immune checkpoint inhibitors and different therapeutic interventions to enhance response rates and overcome immune checkpoint inhibitor resistance. Combining radiotherapy, a primary HNSCC treatment modality, with immunotherapy has been shown to induce potent antitumour immune responses in many cancers including HNSCC. ⋯ In this Series paper, we examine how radiotherapy can be used to its maximum therapeutic potential in the setting of immunotherapy treatment for HNSCC by focusing on published clinical and preclinical data. We rely on preclinical evidence for this disease to discuss how radiotherapy can help create and maintain an immunologically permissive environment. Our hope is that such mechanistic insights will provide a foundation for maximising the use of radioimmunotherapy in disease control, designing future trials, interpreting emerging immunotherapy data, and accelerating discovery within radioimmunotherapy interventions for HNSCC.
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The lancet oncology · Aug 2019
Observational Study5-year overall survival in patients with lung cancer eligible or ineligible for screening according to US Preventive Services Task Force criteria: a prospective, observational cohort study.
The US Preventive Services Task Force (USPSTF) recommends lung cancer screening among individuals aged 55-80 years with a 30 pack-year cigarette smoking history and, if they are former smokers, those who quit within the past 15 years. Our previous report found that two-thirds of newly diagnosed patients with lung cancer do not meet these criteria; they are reported to be either long-term quitters (≥15 years since quitting) or from a younger age group (age 50-54 years). We aimed to assess survival outcomes in these two subgroups. ⋯ National Institutes of Health and the Mayo Clinic Foundation.