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Targeted Oncology

Emma D Deeks
Cabozantinib is an inhibitor of multiple receptor tyrosine kinases (RTKs) with roles in cancer pathogenesis. This review focuses on data relevant to the use of cabozantinib tablets (Cabometyx® ) in the treatment of hepatocellular carcinoma (HCC) in patients who have been previously treated with the multi-RTK inhibitor sorafenib, an indication for which cabozantinib tablets are approved in the EU and USA. Approval of cabozantinib in this setting was based largely on the findings of CELESTIAL, a phase 3 trial in adults with advanced HCC who had previously received sorafenib, had progressive disease after at least one systemic therapy and had received up to two systemic treatments for their advanced disease...
February 14, 2019: Targeted Oncology
Maja J A de Jonge, Neeltje Steeghs, Martijn P Lolkema, Sebastien J Hotte, Hal W Hirte, Diane A J van der Biessen, Albiruni R Abdul Razak, Filip Y F L De Vos, Remy B Verheijen, David Schnell, Linda C Pronk, Monique Jansen, Lillian L Siu
BACKGROUND: Overexpression/activation of focal adhesion kinase (FAK) in human malignancies has led to its evaluation as a therapeutic target. We report the first-in-human phase I study of BI 853520, a novel, potent, highly selective FAK inhibitor. OBJECTIVE: Our objectives were to identify the maximum tolerated dose (MTD), and to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD), biomarker expression, and preliminary activity. PATIENTS AND METHODS: The study comprised a standard 3 + 3 dose-escalation phase followed by an expansion phase in patients with selected advanced, nonhematologic malignancies...
February 11, 2019: Targeted Oncology
Remy B Verheijen, Diane A J van der Biessen, Sebastien J Hotte, Lillian L Siu, Anna Spreafico, Maja J A de Jonge, Linda C Pronk, Filip Y F L De Vos, David Schnell, Hal W Hirte, Neeltje Steeghs, Martijn P Lolkema
BACKGROUND: BI 853520 is a potent inhibitor of focal adhesion kinase and is currently under clinical development for the treatment of non-hematological malignancies. OBJECTIVE: The objective of this study was to evaluate the effect of food and liquid dispersion on the pharmacokinetics of BI 853520 in two open-label, crossover substudies. PATIENTS AND METHODS: Sixteen patients with advanced solid tumors were enrolled in each substudy. The order of administration was randomized, and pharmacokinetic samples were collected for 48 h after administration of a 200 mg dose of BI 853520...
February 11, 2019: Targeted Oncology
Toshihiko Doi, James Chih-Hsin Yang, Kohei Shitara, Yoichi Naito, Ann-Lii Cheng, Akiko Sarashina, Linda C Pronk, Yoshito Takeuchi, Chia-Chi Lin
BACKGROUND: Focal adhesion kinase (FAK) inhibitors have demonstrated anti-tumor activity preclinically and are currently being evaluated in humans. A first-in-human study evaluating the novel FAK inhibitor BI 853520 in a predominantly Caucasian population with advanced or metastatic non-hematologic malignancies demonstrated acceptable tolerability and favorable pharmacokinetics. OBJECTIVE: This study was undertaken to investigate the safety, tolerability, and maximum tolerated dose (MTD) of BI 853520 in Japanese and Taiwanese patients with advanced solid tumors...
February 6, 2019: Targeted Oncology
Albert Font, Raquel Luque, José Carlos Villa, Montse Domenech, Sergio Vázquez, Enrique Gallardo, Juan Antonio Virizuela, Carmen Beato, Rafael Morales-Barrera, Antoni Gelabert, Sonia Maciá, Javier Puente, Gustavo Rubio, Xavier Maldonado, Begoña Perez-Valderrama, Alvaro Pinto, Ovidio Fernández Calvo, Enrique Grande, Javier Garde-Noguera, Eva Fernández-Parra, José Ángel Arranz
Bladder cancer is the fourth most common cancer in men and the ninth most common in women in the Western world. The management of bladder carcinoma requires a multidisciplinary approach. Optimal treatment depends on several factors, including histology, stage, patient status, and possible comorbidities. Here we review recent findings on the treatment of muscle-invasive bladder carcinoma, advanced urothelial carcinoma, upper tract urothelial carcinoma, non-urothelial carcinoma, and urologic complications arising from the disease or treatment...
January 29, 2019: Targeted Oncology
Li Chia Chong, Amanda Rose Townsend, Joanne Young, Amitesh Roy, Cynthia Piantadosi, Jennifer E Hardingham, David Roder, Christos Karapetis, Robert Padbury, Guy Maddern, James Moore, Timothy Jay Price
BACKGROUND: Microsatellite instability (MSI) is the molecular marker for DNA mismatch repair deficiency (dMMR) in colorectal cancer (CRC) and has been associated with better survival outcomes in early stage disease. In metastatic CRC (mCRC), outcomes for patients with MSI are less clear. There is evolving evidence that treatment pathways for MSI CRC should include programmed-death 1 (PD-1) antibodies. OBJECTIVE: An analysis was performed to explore the impact of MSI status on overall survival (OS) in mCRC...
January 18, 2019: Targeted Oncology
Zhuanglin Li, Mingxue Wang, Xuejing Yao, Wenting Luo, Yaocheng Qu, Deling Yu, Xue Li, Jianmin Fang, Changjiang Huang
BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is common in pancreatic cancer and associated with the poor prognosis of this malignancy. OBJECTIVE: To develop anti-EGFR antibody-drug conjugates (ADCs) for use in a novel EGFR-targeting approach to treat pancreatic cancer. METHODS: A humanized anti-EGFR monoclonal antibody (RC68) was generated by mouse immunization and complementary-determining region grafting technology...
January 11, 2019: Targeted Oncology
Ilya Tsimafeyeu, Pavel Borisov, Ahmed Abdelgafur, Roman Leonenkov, Olga Novikova, Irina Guseva, Marina Demchenkova, Nadezhda Mikhailova, Andrey Semenov, Zakhar Yurmazov, Irina Sivunova, Madina Ramazanova, Sergey Gamayunov, Dmitry Kosov, Gennady Bratslavsky
BACKGROUND: Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in the phase 3 AXIS study, where 75% of patients had intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk. OBJECTIVE: In this phase 2 study (FavorAx), we assessed the activity of axitinib in mRCC patients with a favorable risk and history of prior vascular endothelial growth factor receptor (VEGFR)-directed therapy...
January 3, 2019: Targeted Oncology
Maximilian J Hochmair, Anna Buder, Sophia Schwab, Otto C Burghuber, Helmut Prosch, Wolfgang Hilbe, Agnieszka Cseh, Richard Fritz, Martin Filipits
BACKGROUND: Acquired epidermal growth factor receptor (EGFR) T790M mutation is the primary resistance mechanism to first-generation EGFR tyrosine kinase inhibitors (TKIs) used in advanced, EGFR mutation-positive non-small-cell lung cancer (NSCLC). Available data, predominantly in Asian patients, suggest that this mutation is also the major cause of resistance to the irreversible ErbB family blocker, afatinib. For EGFR T790M-positive patients who progress on EGFR TKI therapy, osimertinib is an effective treatment option...
December 12, 2018: Targeted Oncology
Sarah Sammons, Noah S Kornblum, Kimberly L Blackwell
The article Fulvestrant-Based Combination Therapy for Second-Line Treatment of Hormone Receptor-Positive Advanced Breast Cancer, written by Sarah Sammons, Noah S. Kornblum and Kimberly L. Blackwell, was originally published electronically on the publisher's internet portal (currently SpringerLink).
December 8, 2018: Targeted Oncology
Harsh Shah, Ulka Vaishampayan
With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole...
December 7, 2018: Targeted Oncology
Quirine F Manson, Natalie D Ter Hoeve, Horst Buerger, Cathy B Moelans, Paul J van Diest
BACKGROUND: Male breast cancer is rare, as it represents less than 1% of all breast cancer cases. In addition, male breast cancer appears to have a different biology than female breast cancer. Programmed death-1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1), seem to have prognostic and predictive values in a variety of cancers, including female breast cancer. However, the role of PD-1 and PD-L1 expression in male breast cancer has not yet been studied. OBJECTIVES: To compare PD-1 and PD-L1 expression in male breast cancer to female breast cancer and to evaluate prognostic values in both groups...
December 5, 2018: Targeted Oncology
Vasilios Karavasilis, Epaminontas Samantas, Georgia-Angeliki Koliou, Anna Kalogera-Fountzila, George Pentheroudakis, Ioannis Varthalitis, Helena Linardou, Grigorios Rallis, Maria Skondra, Georgios Papadopoulos, George Papatsibas, Joseph Sgouros, Athina Goudopoulou, Konstantine T Kalogeras, Christos Dervenis, Dimitrios Pectasides, George Fountzilas
BACKGROUND: The prognosis of patients with advanced pancreatic cancer is dismal, and there is a need for novel and effective treatments. OBJECTIVES: Tο determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a novel gemcitabine (G) and temsirolimus (T) combination (phase I) and estimate the 6-month progression-free survival (PFS) in patients treated with the T + G combination (phase II). PATIENTS AND METHODS: Eligible patients with histologically confirmed inoperable or metastatic pancreatic carcinoma (MPC) were entered into the trial...
November 28, 2018: Targeted Oncology
Young-A Heo, Sohita Dhillon
Olaparib (Lynparza®), a first-in-class poly (ADP-ribose) polymerase (PARP) inhibitor, has recently been approved in a new tablet formulation as maintenance treatment for recurrent high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in complete or partial response to platinum-based chemotherapy. Relative to an earlier capsule formulation, the tablet formulation of olaparib has improved bioavailability, thereby reducing pill burden and offering a more convenient dosage regimen...
December 2018: Targeted Oncology
Helena Verdaguer, Alvaro Arroyo, Teresa Macarulla
Only a limited number of therapeutic strategies are available for patients diagnosed with pancreatic adenocarcinoma, and disease recurrence and mortality are consequently high. For metastatic disease, two combinations are approved in the first line setting: a triplet with 5-fluoruracil, irinotecan, and oxaliplatin, and the combination of gemcitabine and nab-paclitaxel. In patients who have progressed on gemcitabine, a new nanoliposomal formulation of irinotecan has recently been approved. While these treatments have demonstrated some efficacy, there has been little increase in survival rates for metastatic pancreatic cancer patients...
November 23, 2018: Targeted Oncology
Irene Eriksson, Björn Wettermark, Kjell Bergfeldt
BACKGROUND: Although olaparib, the first poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor approved, has been used in routine clinical practice for over three years, little has been published on its uptake, utilization patterns, and clinical outcomes. OBJECTIVE: To examine real-world use and outcomes of olaparib treatment in Swedish patients during the first three years following regulatory approval. PATIENTS AND METHODS: This is a population-based cohort study using data from the Swedish national registers...
November 16, 2018: Targeted Oncology
Lucy Swift, Aarthi Jayanthan, Yibing Ruan, Ronald Anderson, Jessica Boklan, Tanya Trippett, Aru Narendran
BACKGROUND: Leukemia accounts for 30% of all childhood cancers and although the survival rate for pediatric leukemia has greatly improved, relapse is a major cause of treatment failure. Therefore, the development and introduction of novel therapeutics to treat relapsed pediatric leukemia is urgently needed. The proteasome inhibitor bortezomib has been shown to be effective against adult hematological malignancies such as multiple myeloma and lymphoma, but is frequently associated with the development of resistance...
November 16, 2018: Targeted Oncology
Martin Chopra
No abstract text is available yet for this article.
November 13, 2018: Targeted Oncology
Xia Yang, Jia Rao, Wentao Yang, Ruohong Shui
BACKGROUND: Stromal tumor-infiltrating lymphocytes (sTILs) have been identified as a predictive biomarker for response to neoadjuvant chemotherapy (NAC) and prognosis in human epidermal growth factor receptor 2 (HER2)-positive breast cancers. However, standardized scoring methods for use in clinical practice need to be established, and the optimal threshold of sTILs to predict pathological complete response (pCR) and prognosis in HER2+ breast cancers has not yet been defined. OBJECTIVE: The predictive and prognostic values of sTILs in patients with HER2-positive breast cancer treated with NAC were evaluated, with the aim to explore the optimal thresholds of sTILs and to investigate the feasibility of scoring methods in clinical practice...
November 7, 2018: Targeted Oncology
Ondrej Fiala, Veronika Veskrnova, Renata Chloupkova, Alexandr Poprach, Igor Kiss, Katerina Kopeckova, Ladislav Dusek, Lubomir Slavicek, Milan Kohoutek, Jindrich Finek, Marek Svoboda, Lubos Petruzelka, Ludmila Boubliková, Josef Dvorak, Bohuslav Melichar, Tomas Buchler
BACKGROUND: The addition of monoclonal antibodies targeting the epidermal growth factor receptor (anti-EGFR Abs) to chemotherapy for metastatic colorectal carcinoma (mCRC) is commonly delayed in the real-world clinical practice, usually because of late RAS testing results. OBJECTIVE: To determine whether delayed addition of anti-EGFR mAbs up to the fourth cycle of backbone chemotherapy adversely affected outcomes of mCRC patients treated with first-line regimens...
October 23, 2018: Targeted Oncology
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