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Livorno, Italy

Hirsch F.R.,Aurora University | Janne P.A.,Dana-Farber Cancer Institute | Eberhardt W.E.,German Cancer Research Center | Cappuzzo F.,Instituto Toscano Tumori | And 11 more authors.
Journal of Thoracic Oncology

Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. Copyright © 2013 by the International Association for the Study of Lung Cancer. Source

Landi L.,Instituto Toscano Tumori | Cappuzzo F.,Instituto Toscano Tumori
Drugs of Today

Non-small cell lung cancer (NSCLC) represents the paradigm of personalized treatment in human cancer. Several oncogenic alterations with druggable potential have been identified, with ALK rearrangements representing one of the newest and most appealing. Crizotinib is now recognized as the standard of care in chemotherapy-pretreated ALK-positive NSCLC due to the positive results of a recently published trial. Unfortunately, no patient exposed to crizotinib can be cured, and after a median time of 1 year, resistance inevitably occurs. Overcoming resistance is the major challenge in clinical oncology and many molecules are currently under evaluation, including ceritinib (LDK-378). Ceritinib is an oral, potent, second-generation ALK inhibitor recently approved by the U.S. Food and Drug Administration. Preclinical data showed impressive antitumor activity against crizotinib-resistant clones, and based on available data, ceritinib could represent a suitable option in crizotinib-resistant NSCLC. Copyright © 2014 Prous Science, S.A.U. or its licensors. All rights reserved. Source

Mislang A.R.,Instituto Toscano Tumori | Biganzoli L.,Instituto Toscano Tumori

Defining optimal adjuvant treatment for older women with breast cancer is challenged by the lack of level-1 clinical evidence and the heterogeneity of the older population. Nevertheless, recommendations based on reviews of available evidence mainly from retrospective subgroup analyses and extrapolation of study results from younger patients, and expert opinions, may be useful to guide treatment decisions in fit patients. But how can we properly define a “fit” older patient? In clinical practice, age by itself and clinical impression generally drive treatment decision, although the appropriateness of this judgment is under-documented. Such an approach risks overtreatment or, more frequently, undertreatment. A geriatric assessment can be valuable in oncology practice to address this issue. In this review article, we will focus only on systemic treatment and will discuss “standard” adjuvant systemic treatment strategies for fit older breast cancer patients and the role of “personalized” systemic therapy in unfit patients. The concepts conveyed in this review cannot be extrapolated to locoregional therapy. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source

Hart C.D.,Instituto Toscano Tumori | Galardi F.,Translational Research Laboratory | De Luca F.,Translational Research Laboratory | Pestrin M.,Instituto Toscano Tumori | Di Leo A.,Instituto Toscano Tumori
Current Breast Cancer Reports

Circulating tumour cells (CTCs) in breast cancer offer a unique opportunity to sample tissue that can derive from multiple sites in the body and may be more representative of the whole disease than a single standard biopsy. Their presence is now clearly associated with worse prognosis and can indicate treatment failure. Improved techniques to isolate single CTCs have also permitted in-depth molecular studies, revealing marked heterogeneity. Whilst giving a novel window into tumour evolution and resistance, it also raises new questions regarding treatment approaches. The ongoing challenge remains the translation of new information gleaned from CTCs into clinical benefit. © Springer Science+Business Media New York 2015. Source

Hart C.D.,Instituto Toscano Tumori | Migliaccio I.,Instituto Toscano Tumori | Malorni L.,Instituto Toscano Tumori | Guarducci C.,Instituto Toscano Tumori | And 2 more authors.
Nature Reviews Clinical Oncology

Hormone-receptor-positive breast cancer accounts for the majority - up to 80% - of all breast cancers. The evolution of breast cancer from early stage to the metastatic setting leads to increased heterogeneity, the occurrence of new mutations, and the development of treatment resistance representing a great challenge for management decisions. Unfortunately, little data exist to offer guidance in this context, and a reliance on traditional clinical parameters remains when deciding on optimal treatment. In advanced-stage oestrogen receptor-positive (ER+) disease, ongoing issues include the choice between endocrine therapy and chemotherapy, the appropriate sequence of treatment agents, and the incorporation of biological agents, such as everolimus, into the treatment armamentarium. In metastatic disease, repeated biopsies can help to reassess the receptor or genetic mutational status; however, the evidence to support this approach is limited. In this Review, we examine the current evidence that can guide treatment decisions in patients with advanced-stage ER+ breast cancer, discuss how to tackle these therapeutic challenges and provide suggestions for the optimal management of this patient population. © 2015 Macmillan Publishers Limited. Source

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