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Targeted Oncology

Hiroki Ishihara, Toshio Takagi, Tsunenori Kondo, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Kazunari Tanabe
BACKGROUND: Sarcopenia is a state of degenerative skeletal muscle wasting induced by cancer cachexia. OBJECTIVE: To evaluate the prognostic impact of changes in skeletal muscle mass (SMM) during first-line sunitinib therapy on oncological outcomes in metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Sixty-nine patients were evaluated retrospectively. The skeletal muscle index (SMI) was calculated based on computed tomography images obtained before the initiation (pre-treatment SMI) and after two cycles of sunitinib treatment (post-treatment SMI)...
October 16, 2018: Targeted Oncology
Francesco Massari, Vincenzo Di Nunno, Lidia Gatto, Matteo Santoni, Riccardo Schiavina, Laura Cosmai, Eugenio Brunocilla, Andrea Ardizzoni, Camillo Porta
BACKGROUND: Cytoreductive nephrectomy in metastatic renal cell carcinoma (mRCC) patients has been common clinical practice due to evidence that resection of the primary tumor results in a survival benefit regardless of systemic treatment. Recently, the first large phase III randomized, non-inferiority prospective clinical trial evaluating this surgical approach demonstrated that systemic treatment alone was not inferior to primary surgery plus systemic treatment. OBJECTIVE: Our aim was to evaluate if cytoreductive nephrectomy results in a survival benefit over systemic treatment alone in patients with mRCC and in specific subgroups, including patients with brain metastases, poor performance status, poor prognosis according to IMDC or MSKCC criteria, and clear cell and non-clear cell histologies...
October 15, 2018: Targeted Oncology
Giovanni Fucà, Giulia Galli, Marta Poggi, Giuseppe Lo Russo, Claudia Proto, Martina Imbimbo, Milena Vitali, Monica Ganzinelli, Claudia Lanti, Giuliano Molino, Fabiano Stangoni, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino, Diego Signorelli
BACKGROUND: A consistent percentage of patients with metastatic non-small cell lung cancer (NSCLC) derives no or only marginal benefit from immunotherapy (IO). OBJECTIVE: Since serum sodium has been linked to both prognosis in NSCLC and modulation of immune cells activity, we aimed to assess the association between low baseline serum sodium concentration (≤ 135 mEq/L) and clinical outcomes of patients with metastatic NSCLC treated with IO. PATIENTS AND METHODS: We included metastatic NSCLC patients treated with checkpoint inhibitors in our department from April 2013 to April 2018 with available baseline serum sodium concentration...
October 10, 2018: Targeted Oncology
Bo Zhang, Yanwei Zhang, Jianlin Xu, Xueyan Zhang, Tianqing Chu, Shuyuan Wang, Jie Qian, Rong Qiao, Jun Lu, Lele Zhang, Baohui Han
BACKGROUND: Oncogenic fusion genes consisting of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) can be detected in 5-7% of lung adenocarcinoma cases. The prevalence of ALK rearrangement in non-adenocarcinoma, non-small cell lung cancers (NA-NSCLC) is currently unknown. In addition, the efficacy of crizotinib in these patients has not been well established. OBJECTIVES: The aim of this study was to investigate the prevalence of ALK rearrangement in NA-NSCLC patients and the therapeutic efficacy of crizotinib in these patients...
September 14, 2018: Targeted Oncology
Sarah Sammons, Noah S Kornblum, Kimberly L Blackwell
Fulvestrant is recommended for patients with hormone receptor-positive (HR+) advanced breast cancer (ABC) who progress after aromatase inhibitor therapy. As most patients in this setting have already developed mechanisms of resistance to endocrine therapy, targeting biological pathways associated with endocrine resistance in combination with fulvestrant may improve outcomes. Therefore, evidence supporting a combinatorial treatment approach in the second-line setting was investigated based on a search of PubMed and ClinicalTrials...
August 22, 2018: Targeted Oncology
Luis E Raez, Edgardo S Santos
No abstract text is available yet for this article.
October 2018: Targeted Oncology
Alejandro Ruiz-Patiño, Christian David Castro, Luisa María Ricaurte, Andrés F Cardona, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Beatriz Wills, Noemí Reguart, Hernán Carranza, Carlos Vargas, Jorge Otero, Luis Corrales, Claudio Martín, Pilar Archila, July Rodriguez, Jenny Avila, Melissa Bravo, Luis Eduardo Pino, Rafael Rosell, Oscar Arrieta
BACKGROUND: Non-small cell lung cancer (NSCLC) has a 5-year survival of 5-16%. Epidermal growth factor receptor (EGFR) mutations, in most cases, confer sensitivity to EGFR tyrosine kinase inhibitor (TKI) therapy. Nonetheless, it is still unclear why clinical outcomes vary among patients with identical EGFR mutations. The amplification of the EGFR gene (EGFRamp) may play a significant role. OBJECTIVE: Compare the complete (CR) and partial response (PR) rates, overall survival (OS), and progression-free survival (PFS) in Hispanic patients with lung adenocarcinoma treated with erlotinib with EGFR mutations (L858R or exon 19 deletion [Del19]) with and without concomitant EGFRamp...
October 2018: Targeted Oncology
Shivaani Kummar, Ulrik N Lassen
Oncogenic somatic chromosomal rearrangements involving the NTRK1, NTRK2 or NTRK3 genes (NTRK gene fusions) occur in up to 1% of all solid tumors, and have been reported across a wide range of tumor types. The fusion proteins encoded by such rearranged sequences have constitutively activated TRK tyrosine kinase domains, providing novel therapeutic anticancer targets. The potential clinical effectiveness of TRK inhibition in patients with tumors harboring NTRK gene fusions is being assessed in phase I and II trials of TRK inhibitors, such as larotrectinib and entrectinib...
October 2018: Targeted Oncology
Alice Tzeng, C Marcela Diaz-Montero, Patricia A Rayman, Jin S Kim, Paul G Pavicic, James H Finke, Pedro C Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S Ernstoff, Christopher J Hoimes, Brian I Rini, Jorge A Garcia, Timothy D Gilligan, Moshe C Ornstein, Petros Grivas
BACKGROUND: The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE: We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC)...
October 2018: Targeted Oncology
Annelieke E C A B Willemsen, Lioe-Fee de Geus-Oei, Maaike de Boer, Jolien Tol, Yvonne Kamm, Paul C de Jong, Marianne A Jonker, Allert H Vos, Willem Grootjans, Johannes W B de Groot, Sasja F Mulder, Erik H J G Aarntzen, Winald R Gerritsen, Carla M L van Herpen, Nielka P van Erp
BACKGROUND: Treating breast cancer patients with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses. OBJECTIVE: We investigated whether everolimus exposure and early metabolic response are predictors for toxicity and effectiveness in these patients. PATIENTS AND METHODS: We performed pharmacokinetic assessments 14 and 35 days after starting treatment. [18 F]fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) was performed at baseline, and 14 and 35 days after the start of the therapy...
October 2018: Targeted Oncology
Hiroki Ishihara, Tsunenori Kondo, Toshio Takagi, Hidekazu Tachibana, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Hirohito Kobayashi, Kazunari Tanabe
BACKGROUND: Investigations on rapid disease progression in patients with urologic malignancies treated with immune checkpoint inhibitors are currently lacking. OBJECTIVE: The objective of this study was to assess cases of rapid disease progression/immediate development of progressive disease (immediate PD) in patients with pretreated metastatic renal cell carcinoma (mRCC) treated with nivolumab. PATIENTS AND METHODS: Forty patients were retrospectively evaluated...
October 2018: Targeted Oncology
Marc J Braunstein, John Kucharczyk, Sylvia Adams
The immune system encompasses a broad array of defense mechanisms against foreign threats, including invading pathogens and transformed neoplastic cells. Toll-like receptors (TLRs) are critically involved in innate immunity, serving as pattern recognition receptors whose stimulation leads to additional innate and adaptive immune responses. Malignant cells exploit the natural immunomodulatory functions of TLRs, expressed mainly by infiltrating immune cells but also aberrantly by tumor cells, to foster their survival, invasion, and evasion of anti-tumor immune responses...
October 2018: Targeted Oncology
Roberto Iacovelli, Chiara Ciccarese, Claudia Mosillo, Davide Bimbatti, Emanuela Fantinel, Lisa Stefani, Michele Simbolo, Mario Romano, Renzo Mazzarotto, Matteo Brunelli, Emilio Bria, Aldo Scarpa, Rita T Lawlor, Walter Artibani, Giampaolo Tortora
BACKGROUND: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores. OBJECTIVE: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC. PATIENTS AND METHODS: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR)...
October 2018: Targeted Oncology
Brianna Hoffner, Anthony D Elias, Victor M Villalobos
About 50% of sarcomas have specific pathology-defining molecular alterations including mutations, fusion genes, and gene amplifications. Some of these alterations appear to be oncogenic drivers, and a subset can be utilized as targets for standard or experimental molecularly targeted agents in the clinic. In addition, immunotherapies may have a growing role in the treatment of sarcomas in the future.
October 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...
October 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...
October 2018: 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 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 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...
August 2018: Targeted Oncology
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