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https://www.readbyqxmd.com/read/28523933/the-pazoreal-noninterventional-study-to-assess-effectiveness-and-safety-of-pazopanib-and-everolimus-in-the-changing-metastatic-renal-cell-carcinoma-treatment-landscape
#1
Peter J Goebell, Christian Doehn, Carsten Grüllich, Viktor Grünwald, Thomas Steiner, Rainer Ehneß, Manfred Welslau
VEGFR and mTOR inhibitors are broadly used in metastatic renal cell carcinoma (mRCC) therapy, and sequential first-line pazopanib (VEGFR inhibitor) and second-line everolimus (mTOR inhibitor) is a standard treatment option. Nivolumab and lenvatinib/everolimus combination was recently approved in Europe for use in mRCC after previous therapy. Prospective routine data on sequential therapy including nivolumab and/or lenvatinib are missing. This is a prospective, noninterventional study, which evaluates the effectiveness, tolerability, safety and quality of life following 450 patients with mRCC starting either on pazopanib as first-line therapy or third-line everolimus plus/minus lenvatinib following nivolumab...
May 19, 2017: Future Oncology
https://www.readbyqxmd.com/read/28515249/incorporating-new-systemic-therapies-in-kidney-cancer-treatment
#2
Eric Jonasch
In 2017, pazopanib and sunitinib remain the mainstays of frontline therapy for advanced renal cell carcinoma. Independent review of frontline cabozantinib therapy may alter standard of care for patients at intermediate and poor risk. Multiple agents show a survival advantage in the second-line setting, including nivolumab, cabozantinib, and combination lenvatinib and everolimus. Selection of subsequent therapy will depend on patient disease status, comorbidities, and resource availability.
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28486081/cost-effectiveness-of-lenvatinib-sorafenib-and-placebo-in-the-treatment-of-radioiodine-refractory-differentiated-thyroid-cancer
#3
Leslie Wilson, Wei Huang, Linda Chen, Jie Ting, Vicky Cao
BACKGROUND: Lenvatinib (Lenvima®) and sorafenib (Nexavar®) are the two most recently FDA-approved drugs for treating radioiodine-refractory differentiated thyroid cancer (RR-DTC). Both demonstrated superior progression-free survival over placebo in their respective phase III clinical trials. In this study, we compared the cost-effectiveness of the two treatments with placebo from a limited societal perspective. METHODS: A Markov model was developed to estimate the costs and health benefits for treatment of RR-DTC...
May 9, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28471306/salvage-lenvatinib-therapy-in-metastatic-anaplastic-thyroid-cancer
#4
Nicole M Iniguez Ariza, Mabel Ryder, Crystal R Hilger, Keith C Bible
BACKGROUND: Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only 5 months and <20% 1-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding use of lenvatinib in ATC...
May 4, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28469962/lenvatinib-enhances-the-antitumor-effects-of-paclitaxel-in-anaplastic-thyroid-cancer
#5
Changxin Jing, Zhifei Gao, Rong Wang, Zhao Yang, Bingyin Shi, Peng Hou
Anaplastic thyroid cancer (ATC) is a rare malignancy and has a very poor prognosis due to its aggressive behavior and resistance to treatment. No effective treatment modalities are currently available. Lenvatinib has shown encouraging results in the patients with radioiodine-refractory differentiated thyroid cancer (DTC); however, lenvatinib monotherapy has a relatively low efficacy against ATC. In this study, we assessed the antitumor effects of a combination of lenvatinib and microtubule inhibitor paclitaxel in ATC cells in vitro and in vivo...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28458901/the-management-of-metastatic-radioiodine-refractory-differentiated-thyroid-cancer-requires-an-integrated-approach-including-both-directed-and-systemic-therapies
#6
Shamil D Cooray, Duncan J Topliss
SUMMARY: A 58-year-old man with metastatic radioiodine-refractory differentiated thyroid cancer (DTC) presented with left thigh and right flank numbness. He had known progressive and widespread bony metastases, for which he received palliative radiotherapy, and multiple bilateral asymptomatic pulmonary metastases. CT scan and MRI of the spine revealed metastases at right T10-L1 vertebrae with extension into the central canal and epidural disease at T10 and T11 causing cord displacement and canal stenosis but retention of spinal cord signal...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#7
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28439491/translating-new-data-to-the-daily-practice-in-second-line-treatment-of-renal-cell-carcinoma-the-role-of-tumor-growth-rate
#8
EDITORIAL
Enrique Grande, Olga Martínez-Sáez, Pablo Gajate-Borau, Teresa Alonso-Gordoa
The therapeutic options for patients with metastatic renal cell carcinoma (mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib...
April 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28413394/significant-amelioration-of-tracheal-stenosis-following-lenvatinib-in-a-patient-who-has-anaplastic-thyroid-carcinoma-with-bronchomediastinal-infiltration-a-case-report
#9
Takahiro Fukuhara, Ryohei Donishi, Satoshi Koyama, Naritomo Miyake, Eriko Matsuda, Kazunori Fujiwara, Hiroya Kitano, Hiromi Takeuchi
BACKGROUND: Anaplastic thyroid carcinoma has an extremely poor prognosis, and no known drugs have exhibited acceptable efficacy. In recent years, novel anticancer tyrosine kinase inhibitors have been developed. We encountered a case of tracheal stenosis due to mediastinal and tracheal infiltration of anaplastic carcinoma for which lenvatinib exhibited remarkable effects; owing to this, airway management could be performed, even though the patient's condition was considered critical. CASE REPORT: A 55-year-old man presented with locally advanced anaplastic thyroid carcinoma that was observed to have mediastinal infiltration...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28412971/appraising-the-holistic-value-of-lenvatinib-for-radio-iodine-refractory-differentiated-thyroid-cancer-a-multi-country-study-applying-pragmatic-mcda
#10
Monika Wagner, Hanane Khoury, Liga Bennetts, Patrizia Berto, Jenifer Ehreth, Xavier Badia, Mireille Goetghebeur
BACKGROUND: The objective of the study was to reveal through pragmatic MCDA (EVIDEM) the contribution of a broad range of criteria to the value of the orphan drug lenvatinib for radioiodine refractory differentiated thyroid cancer (RR-DTC) in country-specific contexts. METHODS: The study was designed to enable comprehensive appraisal (12 quantitative, 7 qualitative criteria) in the current disease context (watchful waiting, sorafenib) of France, Italy and Spain...
April 17, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28403496/-interdisciplinary-recommendations-for-the-treatment-of-metastatic-renal-cell-carcinoma
#11
Kurt Miller, Lothar Bergmann, Christian Doehn, Jürgen Gschwend, Ulrich Keilholz
Thanks to the use of targeted therapies, the prognosis of patients with metastatic renal cell carcinoma (mRCC) has improved significantly. A median overall survival of more than 2 years is a realistic claim. These improvements are also reflected in recent discussions about 3 and more lines of therapy.Sunitinib, pazopanib, the combination of bevacizumab and interferon alpha, and temsirolimus are approved for first-line therapy of mRCC. Sunitinib and pazopanib are also approved for second-line therapy, which, for pazopanib, is confined to the use after cytokine failure...
February 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28390289/lenvatinib-an-oral-multi-kinases-inhibitor-associated-hypertension-potential-role-of-vascular-endothelial-dysfunction
#12
Daisuke Sueta, Koichi Suyama, Aiko Sueta, Noriaki Tabata, Takayoshi Yamashita, Mai Tomiguchi, Takashi Takeshita, Mutsuko Yamamoto-Ibusuki, Eiichiro Yamamoto, Yasuhiro Izumiya, Koichi Kaikita, Yutaka Yamamoto, Seiji Hokimoto, Hirotaka Iwase, Kenichi Tsujita
BACKGROUND AND AIMS: Lenvatinib (Lenvima(®)), an oral multi-kinase inhibitor, is effective in the treatment of differentiated thyroid carcinomas (DTCs). A severe adverse effect of lenvatinib is hypertension, thus limiting its use as an anti-cancer treatment. Although the pathogenesis of hypertension is generally assumed to involve microvascular bed reduction and an increase in peripheral vascular resistance due to a decrease in nitrogen oxide (NOx) production after vascular endothelial growth factor (VEGF) inhibition, the effects of hypertension on vascular endothelial function in actual patients remain unclear...
May 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#13
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
June 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28318881/targeted-therapy-in-thyroid-cancer-state-of-the-art
#14
L Valerio, L Pieruzzi, C Giani, L Agate, V Bottici, L Lorusso, V Cappagli, L Puleo, A Matrone, D Viola, C Romei, R Ciampi, E Molinaro, R Elisei
Thyroid cancer typically has a good outcome following standard treatments, which include surgery, radioactive iodine ablation for differentiated tumours and treatment with thyrotropine hormone-suppressive levothyroxine. Thyroid cancers that persist or recur following these therapies have a poorer prognosis. Cytotoxic chemotherapy or external beam radiotherapy has a low efficacy in these patients. 'Target therapy' with tyrosine kinase inhibitors (TKIs) represent an important therapeutic option for the treatment of advanced cases of radioiodine refractory (RAI-R) differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and possibly for cases of poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC)...
March 16, 2017: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/28303494/current-management-strategy-for-metastatic-renal-cell-carcinoma-and-future-directions
#15
REVIEW
Hussein Merza, Marijo Bilusic
PURPOSE OF REVIEW: Major strides have been made in the treatment of kidney cancer in the last several years with checkpoint immunotherapies and novel targeted agents. This manuscript will review current treatment strategies for metastatic renal cell carcinoma and will discuss future directions. RECENT FINDINGS: Most recently, several new drugs including nivolumab, cabozantinib, and a combination of lenvatinib and everolimus have demonstrated acceptable toxicity and significantly improved overall survival, but evidence-based guidelines for sequencing of the approved treatment options and treatment selection based on biomarkers are still missing...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28299283/lenvatinib-for-anaplastic-thyroid-cancer
#16
Makoto Tahara, Naomi Kiyota, Tomoko Yamazaki, Naoko Chayahara, Kenji Nakano, Lina Inagaki, Kazuhisa Toda, Tomohiro Enokida, Hironobu Minami, Yoshinori Imamura, Tatsuya Sasaki, Takuya Suzuki, Katsuki Fujino, Corina E Dutcus, Shunji Takahashi
BACKGROUND: Lenvatinib has been approved by regulatory agencies in Japan, the United States, and the European Union for treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thyroid cancer, however, is a clinically diverse disease that includes anaplastic thyroid cancer (ATC), the subtype associated with the highest lethality. Effective therapy for ATC is an unmet need. PATIENTS AND METHODS: This phase 2, single-arm, open-label study in patients with thyroid cancer, including ATC, RR-DTC, and medullary thyroid cancer was conducted from 3 September 2012 to 9 July 2015...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#17
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28276433/renal-cell-carcinoma
#18
REVIEW
James J Hsieh, Mark P Purdue, Sabina Signoretti, Charles Swanton, Laurence Albiges, Manuela Schmidinger, Daniel Y Heng, James Larkin, Vincenzo Ficarra
Renal cell carcinoma (RCC) denotes cancer originated from the renal epithelium and accounts for >90% of cancers in the kidney. The disease encompasses >10 histological and molecular subtypes, of which clear cell RCC (ccRCC) is most common and accounts for most cancer-related deaths. Although somatic VHL mutations have been described for some time, more-recent cancer genomic studies have identified mutations in epigenetic regulatory genes and demonstrated marked intra-tumour heterogeneity, which could have prognostic, predictive and therapeutic relevance...
March 9, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28252459/renal-cell-carcinoma-molecular-characterization-and-evolving-treatment-paradigms
#19
Mark W Ball, Eric A Singer, Ramaprasad Srinivasan
PURPOSE OF REVIEW: The treatment landscape of advanced renal cell carcinoma (RCC) continues to shift as both new targeted therapies and immunotherapies show efficacy in treating the disease. Contemporary insights into the molecular characterization of RCC are likely to fuel the development of additional therapies. This review summarizes recent advancements in the biologic characterization of RCC and discusses newly approved therapies and ongoing studies in the treatment of advanced RCC...
March 1, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28247252/cabozantinib-an-active-novel-multikinase-inhibitor-in-renal-cell-carcinoma
#20
REVIEW
Nizar M Tannir, Gisela Schwab, Viktor Grünwald
Clear cell renal cell carcinoma (RCC) is characterized by inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL loss drives tumor angiogenesis and accounts for the clinical activity of VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), the first-line standard of care for advanced RCC. Within the last year, three new second-line treatments have received FDA approval for use after anti-angiogenic therapy: the immune checkpoint inhibitor nivolumab, the TKI cabozantinib, and the combination of the TKI lenvatinib and the mTOR inhibitor everolimus...
February 2017: Current Oncology Reports
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