The lancet oncology
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The lancet oncology · Mar 2019
ReviewThe extent of surgery for stage III melanoma: how much is appropriate?
Since the first documented lymph node dissection in 1892, many trials have investigated the potential effect of this surgical procedure on survival in patients with melanoma. Two randomised controlled trials were unable to demonstrate improved survival with completion lymph node dissection versus nodal observation in patients with sentinel node-positive disease, although patients with larger sentinel node metastases (>1 mm) might benefit more from observation than from dissection, and could potentially be considered for adjuvant systemic therapy instead of complete dissection. Adjuvant immunotherapy with high-dose ipilimumab has led to improvements in overall survival, whereas therapy with nivolumab and pembrolizumab has improved relapse-free survival with greater safety. ⋯ Accordingly, existing clinical guidelines are currently being revised. For palpable (macroscopic) nodal disease, the type and extent of surgery could be reduced if the index node can accurately predict the response and if studies show that lymph node dissection can be safely foregone in patients with a complete response. Overall, the appropriate type and extent of surgery for stage III melanoma is changing and becoming more personalised.
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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
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
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).