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Targeted Oncology

Zaina T Al-Salama
The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin (Besponsa® ) is approved in several countries including in the USA, EU and Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin was associated with significantly higher rates of complete remission (including complete remission with incomplete haematological recovery) [CR/CRi] than standard therapy in the pivotal INO-VATE ALL trial...
August 9, 2018: Targeted Oncology
Lorenzo Mortara, Marzia B Gariboldi, Annalisa Bosi, Marco Bregni, Graziella Pinotti, Luigina Guasti, Alessandro Squizzato, Douglas M Noonan, Elena Monti, Leonardo Campiotti
BACKGROUND: Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is frequently added to chemotherapy in the treatment of colon cancer. OBJECTIVE: The present study evaluates the association between vitamin D serum levels and the ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer cell lines...
August 9, 2018: Targeted Oncology
Young-A Heo, Sean T Duggan
Niraparib (Zejula® ), a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for the maintenance treatment of recurrent, epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Approval was based on the results of the randomized, double-blind, placebo-controlled phase III NOVA trial. In NOVA, niraparib significantly prolonged progression-free survival (primary endpoint), chemotherapy-free interval and time to first subsequent therapy compared with placebo in patients with recurrent, platinum-sensitive, high grade serous ovarian, fallopian tube or primary peritoneal cancer...
August 3, 2018: Targeted Oncology
Daniela Femia, Natalie Prinzi, Andrea Anichini, Roberta Mortarini, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Andrea Maurichi, Ilaria Mattavelli, Massimo Milione, Nice Bedini, Ambra Corti, Maria Di Bartolomeo, Filippo de Braud, Sara Pusceddu
Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches...
August 2, 2018: Targeted Oncology
Zipeng Lu, Maximilian Weniger, Kuirong Jiang, Stefan Boeck, Kai Zhang, Alexander Bazhin, Yi Miao, Jens Werner, Jan G D'Haese
Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and is suggested to play a role in the resistance of this deadly disease to systemic treatment. Despite promising results from preclinical studies, clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor (VEGF) and its receptor VEGFR yielded conflicting results. With this systematic review and meta-analysis, we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy...
July 31, 2018: Targeted Oncology
Karima Saboundji, Jean-Bernard Auliac, Maurice Pérol, Géraldine François, Henri Janicot, Marie Marcq, Catherine Dubos-Arvis, Aldo Renault, Florian Guisier, Luc Odier, Radj Gervais, Christos Chouaïd
BACKGROUND: The prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor. OBJECTIVE: To assess the clinical efficacy of osimertinib, a third-generation tyrosine-kinase inhibitor (TKI), in patients with epidermal growth-factor receptor (EGFR)-mutated NSCLCs and LM. PATIENTS AND METHODS: Retrospective study of NSCLC patients with osimertinib-treated EGFR-mutated NSCLC and LM. RESULTS: Twenty patients (mean age, 61...
July 23, 2018: Targeted Oncology
Michele Ghidini, Jens C Hahne, Melissa Frizziero, Gianluca Tomasello, Francesco Trevisani, Andrea Lampis, Rodolfo Passalacqua, Nicola Valeri
Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer...
July 13, 2018: Targeted Oncology
Marion Ferreira, Eric Pichon, Delphine Carmier, Emilie Bouquet, Cécile Pageot, Theodora Bejan-Angoulvant, Marion Campana, Emmanuelle Vermes, Sylvain Marchand-Adam
Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood...
July 13, 2018: Targeted Oncology
Xihui Wang, Rui Yang, Chunyan Yuan, Yanli An, Qiusha Tang, Daozhen Chen
BACKGROUND: Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach. OBJECTIVE: We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo...
July 10, 2018: Targeted Oncology
Pedro C Barata, Prateek Mendiratta, Brandie Heald, Stefan Klek, Petros Grivas, Davendra P S Sohal, Jorge A Garcia
INTRODUCTION: Tumor profiling by targeted next-generation sequencing (tNGS) and personalized treatment based on these results is becoming increasingly common in patients with metastatic solid tumors, but it remains unclear whether this strategy results in benefit to patients with metastatic prostate cancer (mPCa). OBJECTIVE: To assess the clinical utility of tNGS in treatment decision-making for patients with mPCa. PATIENTS AND METHODS: Patients with available genomic profiling using tumor tissue (FoundationOne, F1) or cell-free DNA (FoundationACT, Guardant360) were included...
July 4, 2018: Targeted Oncology
Mark Agulnik, Steven Attia
Sarcomas encompass a group of rare solid tumors responsible for approximately 1% of all cancer-related deaths in the United States each year. Subtypes include, but are not limited to, soft tissue sarcomas (STS) such as leiomyosarcoma, liposarcoma, pleomorphic sarcoma, and gastrointestinal stromal tumor (GIST). Treatment options for patients with STS vary depending on, among other factors, histological subtype. Data from a mix of phase 2 and phase 3 trials have suggested that the orally available multikinase inhibitor regorafenib may have efficacy in patients with STS who have progressed on previous lines of systemic therapy...
June 21, 2018: Targeted Oncology
Xuanzong Li, Shijiang Wang, Butuo Li, Zhen Wang, Shuheng Shang, Yang Shao, Xindong Sun, Linlin Wang
The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations...
June 16, 2018: Targeted Oncology
Alberto Farolfi, Micaela Petrone, Emanuela Scarpi, Valentina Gallà, Filippo Greco, Claudia Casanova, Lucia Longo, Gennaro Cormio, Michele Orditura, Alessandra Bologna, Laura Zavallone, Jole Ventriglia, Elisena Franzese, Vera Loizzi, Donatella Giardina, Eva Pigozzi, Raffaella Cioffi, Sandro Pignata, Giorgio Giorda, Ugo De Giorgi
BACKGROUND: The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. OBJECTIVE: The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III-IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab...
June 14, 2018: Targeted Oncology
William H Isacoff, Howard A Reber, Rudolph Bedford, William Hoos, Lola Rahib, Alexander Upfill-Brown, Timothy Donahue, O Joe Hines
BACKGROUND: Continuous-infusion 5-fluorouracil (5FU) and calcium leucovorin plus nab-paclitaxel and oxaliplatin have been shown to be active in patients with pancreatic cancer. As a protracted low-dose infusion, 5FU is antiangiogenic, and has synergy with bevacizumab. As shown in the treatment of breast cancer, bevacizumab and nab-paclitaxel are also synergetic. OBJECTIVE: In this paper we retrospectively analyze the survival of 65 patients with advanced pancreatic cancer who were treated with low-dose continuous (metronomic) chemotherapy given in conjunction with conventional anti-VEGF therapy...
June 7, 2018: Targeted Oncology
Matt Shirley
Avelumab (Bavencio® ) is a fully human IgG1 monoclonal antibody that is directed against programmed cell death ligand 1 (PD-L1). Avelumab functions as an immune checkpoint inhibitor and has recently been approved in the USA, the EU and Japan for the treatment of metastatic Merkel cell carcinoma (MCC). It is thus the first therapeutic agent specifically approved for use in this indication, and is approved for use independent of line of treatment. Approval for avelumab in metastatic MCC was based on the two-part, single-arm, phase II trial, JAVELIN Merkel 200...
June 2018: Targeted Oncology
Hannah A Blair
Atezolizumab (TECENTRIQ™), an immune checkpoint inhibitor, is an immunoglobulin G1 monoclonal antibody that binds to programmed death ligand 1 (PD-L1) and blocks its interactions with programmed death 1 and B7.1 receptors. Atezolizumab is approved as monotherapy in several countries worldwide for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy. Approval was based on its clinical benefit in this setting in the phase II POPLAR and phase III OAK trials...
June 2018: Targeted Oncology
Takashi Ikeda, Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Kazuhiko Yoshida, Junpei Iizuka, Kazunari Tanabe
BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors (RECIST) classification, progressive disease (PD) is defined as target lesion growth (TLG), unequivocal non-target lesion growth (NTLG), or new lesion appearance (NLA). The prognostic impact of the components of PD in tyrosine kinase inhibitor (TKI) therapy for metastatic renal cell carcinoma (mRCC) remains unknown. OBJECTIVE: We retrospectively evaluated the prognostic impact of these PD components on survival in patients with mRCC after first-line TKI therapy...
June 2018: Targeted Oncology
Maximilian Hochmair
Brain metastases and/or leptomeningeal disease (LMD) with associated central nervous system (CNS) metastases are known complications of advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). It is important, therefore, to assess the activity of EGFR tyrosine kinase inhibitors (TKIs) versus such CNS complications. This review explores the literature reporting the intracranial activity of EGFR TKIs, and finds that there is evidence for varying efficacy of the approved agents, erlotinib, gefitinib, afatinib, and osimertinib in patients with CNS metastases...
June 2018: Targeted Oncology
Federico Nichetti, Antonio Marra, Francesca Corti, Alessandro Guidi, Alessandra Raimondi, Natalie Prinzi, Filippo de Braud, Sara Pusceddu
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors...
June 2018: Targeted Oncology
Lotte M Knapen, Rutger H T Koornstra, Johanna H M Driessen, Bas van Vlijmen, Sander Croes, Stein Schalkwijk, Angela Colbers, Winald R Gerritsen, David M Burger, Frank de Vries, Nielka P van Erp
BACKGROUND: The impact of dose and simultaneous use of acid-reducing agents (ARAs) on the effectiveness of vemurafenib is unknown. OBJECTIVES: To determine the association between progression of metastatic BRAF V600 mutated melanoma and (1) dose reductions of vemurafenib and (2) simultaneous use of vemurafenib and ARAs. PATIENT AND METHODS: A retrospective cohort study of 112 first-line vemurafenib users for melanoma was conducted (March 2012-March 2016), using electronic patient records and pharmacy dispensing records of a Dutch academic hospital...
June 2018: Targeted Oncology
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