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https://www.readbyqxmd.com/read/28105863/the-role-of-mtor-inhibition-as-second-line-therapy-in-metastatic-renal-carcinoma-clinical-evidence-and-current-challenges
#1
José Luis González-Larriba, Pablo Maroto, Ignacio Durán, Julio Lambea, Luis Flores, Daniel Castellano
Sequential treatment with targeted agents is the standard of care for patients with metastatic renal cell carcinoma (mRCC). Although first-line therapy with tyrosine kinase inhibitors (TKIs) is recommended for most patients, eventually all patients become resistant to them. Therefore, optimal selection of second-line therapy is crucial. Areas covered: We have reviewed the recent literature through pubmed search and recent congress presentations to briefly describe the clinical evidence for mTOR inhibition as a valid strategy in the treatment of mRCC after progression during anti-VEGFR therapy...
January 20, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28103611/phase-ii-randomised-discontinuation-trial-of-the-met-vegf-receptor-inhibitor-cabozantinib-in-metastatic-melanoma
#2
Adil Daud, Harriet M Kluger, Razelle Kurzrock, Frauke Schimmoller, Aaron L Weitzman, Thomas A Samuel, Ali H Moussa, Michael S Gordon, Geoffrey I Shapiro
BACKGROUND: A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. METHODS: Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS)...
January 19, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28096936/treatment-options-in-advanced-renal-cell-carcinoma-after-first-line-treatment-with-vascular-endothelial-growth-factor-receptor-tyrosine-kinase-inhibitors
#3
REVIEW
Naveen S Basappa
Targeted therapy for metastatic renal cell carcinoma (mRCC) was introduced a decade ago and since then, a number of therapeutic options have been developed. Vascular endothelial growth factor-targeted therapy is the widely accepted first-line option for mRCC. After progression, treatment in the second-line setting has typically been with either axitinib or everolimus. However, with the advent of several new agents demonstrating efficacy in the second-line setting, including nivolumab, cabozantinib, and the combination of lenvatinib and everolimus, the treatment paradigm has shifted toward these novel therapies with improved patient outcomes...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28078236/cabozantinib-in-advanced-renal-cell-carcinoma-a-meteor-impact-on-clinical-practice
#4
EDITORIAL
Paolo Grassi, Elena Verzoni, Alessia Mennitto, Giuseppe Procopio
No abstract text is available yet for this article.
December 2016: Translational Andrology and Urology
https://www.readbyqxmd.com/read/28062674/mixed-results-for-sunitinib-in-renal-cancer
#5
(no author information available yet)
Two studies presented at the European Society for Medical Oncology 2016 Congress evaluated sunitinib in patients with renal cell carcinomas. The first found that the drug prevents recurrence in patients who have had their cancerous kidney removed. The second study suggested that cabozantinib, approved for use as a second-line therapy, works better than sunitinib as a first-line treatment in patients with metastatic renal cell carcinoma.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28035577/c-met-in-chromophobe-renal-cell-carcinoma
#6
Franziska Erlmeier, Philipp Ivanyi, Arndt Hartmann, Michael Autenrieth, Max Wiedemann, Wilko Weichert, Sandra Steffens
c-Met plays a role as a prognostic marker in clear cell renal cell carcinoma. In addition, recently the tyrosine kinase inhibitor cabozantinib targeting c-Met was approved for the treatment of advanced renal cell carcinoma (RCC). In contrast to clear cell RCC, little is known about c-Met expression patterns in rarer RCC subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of c-Met expression on chromophobe (ch)RCC. Patients who underwent renal surgery due to chRCC were retrospectively evaluated...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28024693/the-race-to-target-met-exon-14-skipping-alterations-in-non-small-cell-lung-cancer-the-why-the-how-the-who-the-unknown-and-the-inevitable
#7
REVIEW
Thanyanan Reungwetwattana, Ying Liang, Viola Zhu, Sai-Hong Ignatius Ou
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28013036/the-involvement-of-hgf-met-mmp1-signaling-in-bladder-cancer-invasiveness-and-proliferation-effect-of-the-met-inhibitor-cabozantinib-xl184-on-bladder-cancer-cells
#8
Terumichi Shintani, Yoshito Kusuhara, Kei Daizumoto, Tsogt-Ochir Dondoo, Hiroki Yamamoto, Hidehisa Mori, Tomoya Fukawa, Hiroyoshi Nakatsuji, Tomoharu Fukumori, Masayuki Takahashi, Hiroomi Kanayama
OBJECTIVES: To clarify of the invasive mechanisms of muscle-invasive bladder cancer (MIBC) would be useful for determination of appropriate treatment strategies. We previously showed that HGF-MET signaling is correlated with invasiveness of bladder cancer cells. Here, we investigated the effects of the MET inhibitor, Cabozantinib (XL184), on bladder cancer (BCa) cells METHODS: We first conducted western blot analysis to investigate MET expression in BCa cell lines. Next, we examined the effect of Cabozantinib on their proliferation and invasive abilities using MTT and Matrigel invasion assays, respectively...
December 21, 2016: Urology
https://www.readbyqxmd.com/read/27922668/dual-inhibition-using-cabozantinib-overcomes-hgf-met-signaling-mediated-resistance-to-pan-vegfr-inhibition-in-orthotopic-and-metastatic-neuroblastoma-tumors
#9
Estelle Daudigeos-Dubus, Ludivine Le Dret, Olivia Bawa, Paule Opolon, Albane Vievard, Irène Villa, Jacques Bosq, Gilles Vassal, Birgit Geoerger
MET is expressed on neuroblastoma cells and may trigger tumor growth, neoangiogenesis and metastasis. MET upregulation further represents an escape mechanism to various anticancer treatments including VEGF signaling inhibitors. We developed in vitro a resistance model to pan-VEGFR inhibition and explored the simultaneous inhibition of VEGFR and MET in neuroblastoma models in vitro and in vivo using cabozantinib, an inhibitor of the tyrosine kinases including VEGFR2, MET, AXL and RET. Resistance in IGR-N91-Luc neuroblastoma cells under continuous in vitro exposure pressure to VEGFR1-3 inhibition using axitinib was associated with HGF and p-ERK overexpression...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27909994/cabozantinib-a-review-in-advanced-renal-cell-carcinoma
#10
Zaina T Al-Salama, Gillian M Keating
The multiple tyrosine kinase inhibitor (TKI) cabozantinib (Cabometyx™) is approved in the USA for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the EU, cabozantinib is indicated for the treatment of advanced RCC in adults following prior vascular endothelial growth factor (VEGF)-targeted therapy. In adults with advanced or metastatic clear-cell RCC who had previously received VEGF receptor (VEGFR) TKIs, progression-free survival (PFS) and overall survival (OS) were significantly prolonged in patients who received oral cabozantinib versus oral everolimus in the pivotal METEOR trial...
December 2016: Drugs
https://www.readbyqxmd.com/read/27904650/cabozantinib-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#11
REVIEW
Jose Manuel Ruiz-Morales, Daniel Y C Heng
The treatment of metastatic renal cell carcinoma (mRCC) is rapidly changing. During first-line treatment with targeted therapy, patients ultimately develop resistance to therapy and the disease progresses. Recently, cabozantinib has demonstrated a better response rate, progression-free survival and overall survival compared with everolimus after failure of prior targeted therapy in patients with advanced or metastatic renal cell carcinoma (RCC). Cabozantinib is a small-molecule tyrosine kinase inhibitor (TKI)...
December 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27890466/cabozantinib-improves-clinical-outcomes-in-renal-cancer
#12
Manjulika Das
No abstract text is available yet for this article.
January 2017: Lancet Oncology
https://www.readbyqxmd.com/read/27881454/cabozantinib-is-active-in-patients-with-advanced-ret-rearranged-nsclc
#13
(no author information available yet)
Cabozantinib achieved an overall response rate of 28% in patients with RET-rearranged NSCLC.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27881453/cabozantinib-is-more-effective-than-erlotinib-in-egfr-wild-type-nsclc
#14
(no author information available yet)
Cabozantinib alone or in combination with erlotinib extended survival compared with erlotinib alone.
January 2017: Cancer Discovery
https://www.readbyqxmd.com/read/27879272/quantification-of-pathway-cross-talk-reveals-novel-synergistic-drug-combinations-for-breast-cancer
#15
Samira Jaeger, Ana Igea, Rodrigo Arroyo, Victor Alcalde, Begoña Canovas, Modesto Orozco, Angel R Nebreda, Patrick Aloy
Combinatorial therapeutic approaches are an imperative to improve cancer treatment, because it is critical to impede compensatory signaling mechanisms that can engender drug resistance to individual targeted drugs. Currently approved drug combinations result largely from empirical clinical experience and cover only a small fraction of a vast therapeutic space. Here we present a computational network biology approach, based on pathway cross-talk inhibition, to discover new synergistic drug combinations for breast cancer treatment...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27849399/new-chemical-treatment-options-in-second-line-hepatocellular-carcinoma-what-to-do-when-sorafenib-fails
#16
Hyun Young Woo, So Young Yoo, Jeong Heo
There have been no therapies available for patients who experience disease progression after sorafenib treatment. Regorafenib inhibits multiple kinases involved in tumor proliferation and neoangiogenesis, which has produced a survival benefit in hepatocellular carcinoma (HCC) after sorafenib failure. Other active candidate agents are c-Met inhibitors and immune checkpoint inhibitors. Areas covered: This paper presents an updated summary of the preclinical and clinical experience with regorafenib, c-Met inhibitors (tivantinib, cabozantinib and tepotinib), and a checkpoint inhibitor (nivolumab, pembrolizumab) in HCC...
January 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27842445/cabozantinib-in-genitourinary-malignancies
#17
Tian Zhang, Se Eun Park, Cierra Hong, Daniel J George
Cabozantinib inhibits a variety of cellular receptors including VEGFR1-3, MET, AXL, RET, FLT3 and KIT. These signaling pathways have been shown to be important in genitourinary malignancies. Along its clinical development, it has shown most activity in advanced renal cell carcinoma; the METEOR study compared cabozantinib to everolimus and showed clinically and statistically significant improvements in both progression-free survival and overall survival. Herein, we review the development of cabozantinib in the genitourinary malignancies of renal cell carcinoma, prostate adenocarcinoma and urothelial carcinoma...
November 15, 2016: Future Oncology
https://www.readbyqxmd.com/read/27835047/cabozantinib-for-the-treatment-of-renal-cell-carcinoma
#18
Bernard Escudier, Julie C Lougheed, Laurence Albiges
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy...
November 22, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27825638/erlotinib-cabozantinib-or-erlotinib-plus-cabozantinib-as-second-line-or-third-line-treatment-of-patients-with-egfr-wild-type-advanced-non-small-cell-lung-cancer-ecog-acrin-1512-a-randomised-controlled-open-label-multicentre-phase-2-trial
#19
Joel W Neal, Suzanne E Dahlberg, Heather A Wakelee, Seena C Aisner, Michaela Bowden, Ying Huang, David P Carbone, Gregory J Gerstner, Rachel E Lerner, Jerome L Rubin, Taofeek K Owonikoko, Philip J Stella, Preston D Steen, Ahmed Ali Khalid, Suresh S Ramalingam
BACKGROUND: Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC. METHODS: This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA...
December 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27825636/cabozantinib-in-patients-with-advanced-ret-rearranged-non-small-cell-lung-cancer-an-open-label-single-centre-phase-2-single-arm-trial
#20
Alexander Drilon, Natasha Rekhtman, Maria Arcila, Lu Wang, Andy Ni, Melanie Albano, Martine Van Voorthuysen, Romel Somwar, Roger S Smith, Joseph Montecalvo, Andrew Plodkowski, Michelle S Ginsberg, Gregory J Riely, Charles M Rudin, Marc Ladanyi, Mark G Kris
BACKGROUND: RET rearrangements are found in 1-2% of non-small-cell lung cancers. Cabozantinib is a multikinase inhibitor with activity against RET that produced a 10% overall response in unselected patients with lung cancers. To assess the activity of cabozantinib in patients with RET-rearranged lung cancers, we did a prospective phase 2 trial in this molecular subgroup. METHODS: We enrolled patients in this open-label, Simon two-stage, single-centre, phase 2, single-arm trial in the USA if they met the following criteria: metastatic or unresectable lung cancer harbouring a RET rearrangement, Karnofsky performance status higher than 70, and measurable disease...
December 2016: Lancet Oncology
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