Annals of oncology : official journal of the European Society for Medical Oncology
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Worldwide introduction of the International Fedaration of Gynaecology and Obstetrics (FIGO) 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. ⋯ Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings.
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There is increasing evidence that metastatic colorectal cancer (mCRC) is a genetically heterogeneous disease and that tumours arising from different sides of the colon (left versus right) have different clinical outcomes. Furthermore, previous analyses comparing the activity of different classes of targeted agents in patients with KRAS wild-type (wt) or RAS wt mCRC suggest that primary tumour location (side), might be both prognostic and predictive for clinical outcome. ⋯ This pooled analysis showed a worse prognosis for OS, PFS and ORR for patients with right-sided tumours compared with those with left-sided tumours in patients with RAS wt mCRC and a predictive effect of tumour side, with a greater effect of chemotherapy plus EGFR antibody therapy compared with chemotherapy or chemotherapy and bevacizumab, the effect being greatest in patients with left-sided tumours. These predictive results should be interpreted with caution due to the retrospective nature of the analysis, which was carried out on subpopulations of patients included in these trials, and because none of these studies contemplated a full treatment sequence strategy.
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Glioblastoma (WHO grade IV astrocytoma) is the most frequent primary brain tumor in adults, representing a highly heterogeneous group of neoplasms that are among the most aggressive and challenging cancers to treat. An improved understanding of the molecular pathways that drive malignancy in glioblastoma has led to the development of various biomarkers and the evaluation of several agents specifically targeting tumor cells and the tumor microenvironment. A number of rational approaches are being investigated, including therapies targeting tumor growth factor receptors and downstream pathways, cell cycle and epigenetic regulation, angiogenesis and antitumor immune response. ⋯ The lack of knowledge about relevant molecular drivers in vivo combined with a lack of highly bioactive and brain penetrant-targeted therapies remain significant challenges. In this article, we review the most promising biological insights that have opened the way for the development of targeted therapies in glioblastoma, and examine recent data from clinical trials evaluating targeted therapies and immunotherapies. We discuss challenges and opportunities for the development of these agents in glioblastoma.
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In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. Despite these advances, patient outcomes remain suboptimal, underscoring the need for therapeutic interventions with novel mechanisms of action. The advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for several solid malignancies. ⋯ Other checkpoint inhibitors, including the CTLA-4 inhibitor ipilimumab in combination with several agents, and the PD-L1 inhibitor atezolizumab, are in various stages of clinical development in patients with aRCC. In this review, current evidence related to the clinical use of checkpoint inhibitors for the treatment of patients with aRCC is discussed, including information on the frequency and management of unconventional responses and the management of immune-related adverse events. In addition, perspectives on the future use of checkpoint inhibitors are discussed, including the potential value of treatment beyond progression, the potential use in earlier lines of care or in combination with other agents, and the identification of biomarkers to guide patient selection and enable individualization of therapy.