The lancet oncology
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The lancet oncology · Mar 2019
ReviewImmunotherapy and targeted therapy combinations in metastatic breast cancer.
Immunotherapy is emerging as a new treatment modality in breast cancer. After long-standing use of endocrine therapy and targeted biological therapy, improved understanding of immune evasion by cancer cells and the discovery of selective immune checkpoint inhibitors have created novel opportunities for treatment. ⋯ There is growing interest in the development of combinations of immunotherapy and molecularly targeted therapies for metastatic breast cancer. In this Personal View, we review the available data and ongoing efforts to establish the safety and efficacy of immunotherapeutic approaches in combination with HER2-targeted therapy, inhibitors of cyclin-dependent kinases 4 and 6, angiogenesis inhibitors, poly(ADP-ribose) polymerase inhibitors, as well as chemotherapy and radiotherapy.
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The lancet oncology · Mar 2019
ReviewComparative features and outcomes between paediatric T-cell and B-cell acute lymphoblastic leukaemia.
Contemporary paediatric clinical trials have improved 5-year event-free survival above 85% and 5-year overall survival above 90% in B-cell acute lymphoblastic leukaemia (ALL) in many study groups, whilst outcomes for T-cell ALL are still lagging behind by 5-10% in most studies. Several factors have contributed to this discrepant outcome. First, patients with T-cell ALL are generally older than those with B-cell ALL and, therefore, have poorer tolerance to chemotherapy, especially dexamethasone and asparaginase, and have increased risk of extramedullary relapse. ⋯ Third, T-cell ALL blasts are generally more resistant to conventional chemotherapeutic drugs than are B-cell ALL blasts. Finally, patients with B-cell ALL are more amendable to available targeted therapies, such as Philadelphia chromosome-positive and some Philadelphia chromosome-like ALL cases to ABL-class tyrosine kinase inhibitors, and CD19-positive and CD22-postive B-cell ALL cases to a variety of immunotherapies. Several novel treatments under investigation might narrow the gap in survival between T-cell ALL and B-cell ALL, although novel treatment options for T-cell ALL are limited.
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The lancet oncology · Mar 2019
Randomized Controlled TrialAddition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial.
Abiraterone acetate plus prednisone or prednisolone improves progression-free survival and overall survival in patients with metastatic castration-resistant prostate cancer. Radium-223 improves overall survival and delays the onset of symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases. We assessed concurrent treatment with abiraterone acetate plus prednisone or prednisolone and radium-223 in such patients. ⋯ Bayer.
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The lancet oncology · Mar 2019
Multicenter StudyPembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial.
HER2-positive breast cancers usually contain large amounts of T-cell infiltrate. We hypothesised that trastuzumab resistance in HER2-positive breast cancer could be mediated by immune mechanisms. We assessed the safety and anti-tumour activity of pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, added to trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer. ⋯ Merck, International Breast Cancer Study Group.
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The lancet oncology · Mar 2019
Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020-99: a modelling study.
Cervical screening and human papillomavirus (HPV) vaccination have been implemented in most high-income countries; however, coverage is low in low-income and middle-income countries (LMICs). In 2018, the Director-General of WHO announced a call to action for the elimination of cervical cancer as a public health problem. WHO has called for global action to scale-up vaccination, screening, and treatment of precancer, early detection and prompt treatment of early invasive cancers, and palliative care. An elimination threshold in terms of cervical cancer incidence has not yet been defined, but an absolute rate of cervical cancer incidence could be chosen for such a threshold. In this study, we aimed to quantify the potential cumulative effect of scaled up global vaccination and screening coverage on the number of cervical cancer cases averted over the 50 years from 2020 to 2069, and to predict outcomes beyond 2070 to identify the earliest years by which cervical cancer rates could drop below two absolute levels that could be considered as possible elimination thresholds-the rare cancer threshold (six new cases per 100 000 women per year, which has been observed in only a few countries), and a lower threshold of four new cases per 100 000 women per year. ⋯ National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control (C4; APP1135172).