TAGRISSO (OSIMERTINIB) SHOWS CLINICAL ACTIVITY IN PATIENTS WITH LEPTOMENINGEAL DISEASE FROM LUNG CANCER
AstraZeneca today announced clinical and safety data for Tagrisso (osimertinib) in patients with leptomeningeal (LM) disease, a complication of epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC),1 where cancer cells spread to the cerebrospinal fluid (CSF). LM is a devastating disease associated with advanced lung cancer.
The updated BLOOM Phase I trial results, presented at the American Society of Clinical Oncology (ASCO) annual meeting, showed that irrespective of T790M status of patients, osimertinib led to a change in MRI signal intensity indicative of a reduction in central nervous system (CNS) lesions. 1
Data from 21 patients treated with osimertinib 160mg once daily showed intracranial radiological improvement in seven patients, neurological function improvement in five patients, and clearance of tumour cells from the CSF at two consecutive visits in two patients.1 None of the 21 patients treated with osimertinib received concomitant radiotherapy or intrathecal chemotherapy. Fifteen patients remained on treatment at data cut-off (10 March 2016), of whom seven had been on treatment for more than nine months.1
Further data from the BLOOM study showed that osimertinib crossed the blood-brain barrier. In six of nine patients, a greater than 50% decrease in EGFR mutation level was observed in the CSF up to cycle 9, day 1 of treatment, with a sustained reduction observed in five. These results support previously reported preclinical data demonstrating that osimertinib crosses the blood-brain barrier.2
Dr James CH Yang, from the National Taiwan University Hospital and National Taiwan University Cancer Centre, Taipei, said: “Leptomeningeal disease carries a devastating prognosis, so the safety, tolerability and activity profile seen with osimertinib is encouraging. In the BLOOM study, we saw a decrease in central nervous system lesions in patients with leptomeningeal disease, with accompanying neurological improvement. The results build on previous findings with osimertinib in preclinical and clinical studies and provide evidence of the potential of osimertinib in difficult-to-treat patients who have central nervous system metastases.”
In leptomeningeal disease, cancer cells spread to the membranes surrounding the brain and spinal cord. The disease is currently treated with systemic or intrathecal chemotherapy, whole-brain radiation therapy or EGFR tyrosine kinase inhibitors (TKIs), with median overall survival of 4.5-11 months.3,4 However, most currently-available EGFR-TKIs have limited ability to cross the blood-brain barrier to effectively treat or prevent brain metastases.5-7
Osimertinib 160mg was associated with a manageable tolerability profile over treatment periods up to 11 months. The most common adverse events reported by patients were diarrhoea (58% overall; 5% ≥Grade 3), nausea (48% overall; 0% ≥Grade 3) and rash (43% overall; 0% ≥Grade 3). There were no reported cases of interstitial lung disease, hyperglycaemia or QT prolongation.
Osimertinib recently received accelerated approval as the first indicated treatment for patients with EGFR T790M mutation-positive locally advanced/metastatic NSCLC in the US, EU, Japan and Israel. Osimertinib is also approved in South Korea in the same indication.
AstraZeneca is committed to exploring the full potential of osimertinib in patients with lung cancer, including adjuvant and locally advanced/metastatic first-line EGFRm settings, in patients with and without brain metastases, and in those with leptomeningeal disease.8
– ENDS –
NOTES TO EDITORS
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths and more than breast, prostate and colorectal cancers combined.9 Patients who have the EGFRm form of NSCLC, which occurs in 10-15% of NSCLC patients in Europe10 and 30-40% of NSCLC patients in Asia,11 are particularly sensitive to treatment with currently available EGFR-TKIs, which block the cell signalling pathways that drive the growth of tumour cells.12 However, tumours almost always develop resistance to treatment, leading to disease progression.13 In approximately two-thirds of patients treated with approved EGFR-TKIs such as gefitinib and erlotinib, this resistance is caused by the secondary mutation, T790M.13
About leptomeningeal disease
In leptomeningeal disease, cancer cells spread to the membranes surrounding the brain and spinal cord. It is a complication that affects 3-5% of patients with NSCLC14, and 9% of those with EGFRm NSCLC.15 Treatment is challenging due to poor penetration of the blood-brain barrier by most EGFR-TKI therapies, making it difficult for drugs to reach the brain and spinal cord. 5-7 Average survival in patients with EGFRm NSCLC and leptomeningeal disease is 4.5 to 11 months.3-4 In a recently reported “real-world” retrospective analysis of patients with EGFRm NSCLC treated with EGFR-TKIs, overall survival was approximately 30 months.16
Osimertinib 80mg once-daily tablet is the first medicine indicated for the treatment of adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC. Non-clinical in vitro studies have demonstrated that osimertinib has high potency and inhibitory activity against mutant EGFR phosphorylation across the range of clinically relevant EGFR and T790M mutant NSCLC cell lines with significantly less activity against EGFR in wild-type cell lines.17
Osimertinib is being compared with platinum-based doublet chemotherapy in the confirmatory AURA3 Phase III study in patients with EGFR T790M mutation-positive, locally advanced or metastatic NSCLC who have progressed after EGFR-TKI therapy.18 It is also being investigated in the adjuvant and metastatic first-line settings,19,20 including in patients with and without brain metastases, in leptomeningeal disease,8 and in combination treatment.21
About AstraZeneca in Oncology
AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least 6 new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, we are committed to advance New Oncology as one of AstraZeneca’s six Growth Platforms focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -- immuno-oncology, the genetic drivers of cancer and resistance, DNA damage repair and antibody drug conjugates -- and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and one day eliminate cancer as a cause of death.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - respiratory, inflammation, autoimmune disease (RIA), cardiovascular and metabolic disease (CVMD) and oncology – as well as in infection and neuroscience. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com
1Yang JCH, et al. Osimertinib activity in patients (pts) with leptomeningeal (LM) disease from non-small cell lung cancer (NSCLC): updated results from BLOOM, a Phase I study. Abstract 9002 [Oral Presentation]. Presented at the annual meeting of the American Society of Clinical Oncology, 3-7 June 2016, Chicago, USA.
2 Ballard P, et al. Preclinical activity of AZD9291 in EGFR-mutant NSCLC brain metastases. Presented at the World Congress on Lung Cancer, 6-9 September 2015. Denver, Colorado, USA.
3 Liao BC et al. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for Non-Small-Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis. J Thorac Oncol. 2015;10(12):1754-61.
4 Umemura S et al. Clinical outcome in patients with leptomeningeal metastasis from non-small cell lung cancer: Okayama Lung Cancer Study Group. Lung Cancer. 2012;77(1):134-9.
6 De Vries NA et al. Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs. 2012;30(2):443-9.
7 Zhao J et al. Cerebrospinal fluid concentrations of gefitinib in patients with lung adenocarcinoma. Clin Lung Cancer. 2013 Mar;14(2):188-93.
8 National Institutes of Health. Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors, AZD3759 or AZD9291, in Patients Who Have Advanced Non-Small Cell Lung Cancer (BLOOM). Available at: https://clinicaltrials.gov/ct2/show/NCT02228369?term=AZD9291+brain+met&rank=1. Accessed May 2016.
9 GLOBOCAN (2012). Estimated cancer incidence, mortality and prevalence worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed May 2016.
10 Szumera-Ciećkiewicz A, et al. EGFR mutation testing on cytological and histological samples in non-small cell lung cancer: a Polish, single institution study and systematic review of European incidence. Int J Clin Exp Pathol. 2013;6:2800-12.
11 Ellison G, et al. EGFR mutation testing in lung cancer: a review of available methods and their use for analysis of tumour tissue and cytology samples. J Clin Pathol. 2013;66:79-89.
12 Langer CJ, et al. Epidermal Growth Factor Receptor Inhibition in Mutation-Positive Non-Small-Cell Lung Cancer: Is Afatinib Better or Simply Newer? Journal of Clinical Oncology. 2013;31(27);3303-3305.
13 Yu HA, et al. Analysis of Tumour Specimens at the Time of Acquired Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancer. Clin Cancer Research:2013:19(8):2240-2246.
14 Chamberlain MC, et al. Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy. Arch Neurol. 1998;55(4):506-12.
15 Kuiper JL, et al. Treatment and survival of patients with EGFR-mutated non-small cell lung cancer and leptomeningeal metastasis: A retrospective cohort analysis. Lung Cancer. 2015;89(3):255-61.
16 Inoue A, et al. Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol. 2016;pii: hyw014 [Epub ahead of print].
17 Cross DAE, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4:1046-61.
18 National Institutes of Health. AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (AURA3). Available at: https://clinicaltrials.gov/ct2/show/NCT02151981?term=AURA3&rank=1. Accessed May 2016.
19 National Institutes of Health. AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy (ADAURA). Available at:https://www.clinicaltrials.gov/ct2/show/NCT02511106?term=AZD9291+Versus+Placebo+in+Patients&rank=1. Accessed May 2016.
20 National Institutes of Health. AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA). Available at https://clinicaltrials.gov/ct2/show/NCT02296125?term=FLAURA&rank=1. Accessed May 2016.
21 National Institutes of Health. AZD9291 in Combination With Ascending Doses of Novel Therapeutics. Available at:https://www.clinicaltrials.gov/ct2/show/NCT02143466?term=azd9291&rank=1. Accessed May 2016.
– ENDS –
+44 7842 350541
+44 7880 400690
+44 7818 524012
+46 8 553 260 20
+1 302 885 2677
Thomas Kudsk Larsen
+44 7818 524185
+44 7717 618834
+44 7788 354619
+44 7717 618834
+44 7827 836825
+1 240 543 7970
+1 240 477 3771
Dial / Toll-Free
+1 866 381 7277
Key: RIA - Respiratory, Inflammation and Autoimmunity, CVMD - Cardiovascular and Metabolic Disease, ING - Infection, Neuroscience and Gastrointestinal
Om Business Wire
(c) 2018 Business Wire, Inc., All rights reserved.
Business Wire, a Berkshire Hathaway company, is the global leader in multiplatform press release distribution.
Følg saker fra Business Wire
Registrer deg med din epostadresse under for å få de nyeste sakene fra Business Wire på epost fortløpende. Du kan melde deg av når som helst.
Siste saker fra Business Wire
Emmaus Life Sciences Announces the New England Journal of Medicine has Published the Phase 3 Trial Results of Endari™ (L-Glutamine Oral Powder) in Sickle Cell Disease18.7.2018 21:45 | Pressemelding
VIEW E-MEDIA KIT – Emmaus Life Sciences, Inc. (Emmaus) announced today that the New England Journal of Medicine (NEJM) has published the results of its 48-week phase 3 clinical trial of Endari™ (L-glutamine oral powder) which supported the FDA approval in July 2017 to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. The article reports results that showed significantly fewer sickle cell crises in those receiving Endari compared to placebo by 25 percent; p=0.005 (median 3 vs. median 4) and significantly fewer hospitalizations by 33 percent; p=0.005 (median 2 vs. median 3). Additional findings showed lower cumulative days in hospital of 41 percent; p=0.02 (median 6.5 days vs. median 11 days) and a lower incidence of acute chest syndrome (ACS) by more than 60 percent; p=0.003 (13 of 152 patients [8.6%] had at least 1 ACS compared with 18 of 78 in the placebo group [23.1%]). The most common adverse reactions, occurring in great
Tigo Releases State-of-the-art Wireless Technology – Mesh – as the New Solar Communication Architecture for the TS4 Platform18.7.2018 19:41 | Pressemelding
Tigo®, pioneer of the smart modular Flex MLPE platform, today announced the release of its new Mesh communication architecture. This state-of-the-art wireless technology directly translates to customer benefits – including simplifying the solar design process and accelerating the commissioning steps. The complete Tigo solution uses a simple yet powerful data collection technology that covers the widest ranges of residential & commercial installations at the lowest cost. With Mesh and the recently announced Tigo Access Point (TAP), customers eliminate the need to address any roof obstruction or orientation constraint. To learn more about Mesh and TAP, register for Tigo’s free, online webinar “The Future of Solar is Wireless” on Wednesday July 25th, 2018 at 10am PDT. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20180718005827/en/ Mesh is Tigo's proprietary software that allows each TS4 unit to act as a repeater, extending the
ViiV Healthcare Shares Data from Landmark 2-Drug Regimen Trials At AIDS 201818.7.2018 17:21 | Pressemelding
ViiV Healthcare, the global specialist HIV company majority owned by GSK, with Pfizer Inc. and Shionogi Limited as shareholders, will be presenting over 20 abstracts, including data from the landmark GEMINI 1 & 2 clinical trials, at the 22nd International AIDS Conference (AIDS 2018), 23-27 July 2018, in Amsterdam, The Netherlands. The data being presented this year has a strong focus on novel exploratory therapeutic options and innovative treatment strategies, as well as improving awareness and understanding of key issues that continue to affect the HIV community. John C Pottage, Jr, MD, Chief Scientific and Medical Officer, ViiV Healthcare, commented, “As we see advancements in the treatment options available to people living with HIV, our research efforts over the past few years have been focused on moving beyond viral load and addressing some of the unresolved issues that people living with HIV face, such as the potential long-term risks and toxicities that can be associated with li
Xilam: H1 2018 Revenue: +50%18.7.2018 16:00 | Pressemelding
Regulatory News: The Xilam Group (Paris:XIL) posted consolidated H1 2018 revenue of EUR 13,866 thousand, an increase of 50%. This increase represents an excellent performance, as it follows on the heels of growth of 54% in H1 2017. Revenue for the first part of this financial year breaks down as follows. In thousands of euros 30.06.2018 (1) 30.06.2017 Change New productions 8,465 4,571 +85% Catalogue 5,385 4,652 +16% Other 16 16 +0% Revenue and subsidies 13,866 9,239 +50% (1) Unaudited data. Remarkable success for new releases +85% Excellent H1 growth was driven by the two main businesses, New Productions and Catalogue. In New Productions, H1 deliveries generated record revenue of EUR 8,465 thousand, an 85% increase compared with H1 2017, and confirmed Xilam’s position as a major European animation company. Catalogue revenue was up 16% compared with H1 2017, thanks again to traditional TV channels and digital platforms, in both France and abroad. A fast-paced delivery schedule Thanks t
Department for International Trade: Life Sciences at the Heart of UK Economy18.7.2018 12:38 | Pressemelding
The Government will today (Wednesday 18 July) host the second in a series of roundtables with stakeholders from key life science businesses, demonstrating the importance of the sector to the UK economy. The Chancellor, International Trade Secretary, Business Secretary and Health and Social Care Secretary will be amongst those that meet with senior representatives from leading UK and international life sciences companies as the UK positions itself as the global home of health innovation, welcoming overseas investment and seeking to boost exports in the process. Discussions at the roundtable will focus on how the future of the Life Sciences sector will be supported by the delivery of our modern Industrial Strategy, ensuring that the UK is ‘open for business’ with a positive business environment, our ambitions for a comprehensive agreement with the EU on our future relationship and the development and implementation of our independent trade policy. To date, the government has engaged sign
Universal Laser Systems Expands Its Materials Database with 3M, Victrex and Dexmet Materials18.7.2018 12:05 | Pressemelding
Universal Laser Systems (ULS) announces the addition of 3M™, Victrex® and Dexmet materials to its materials database, the most extensive repository of laser material processing parameters for materials in the range of 10 watts to 500 watts. The 3M, Victrex and Dexmet materials new to the ULS materials database were specifically added for laser processing with the ULTRA and XLS platforms, suited for high accuracy and precision laser cutting, laser ablation and laser surface modification. The materials include: 3M™ Extreme Sealing Tape 4412N 3M™ Thermally Conductive Silicone Interface Pad 5516 Victrex® APTIV® PEEK Film Dexmet PolyGrid® 8PTFE10-125ST Expanded PTFE Dexmet MicroGrid® AL 25 Expanded Aluminum Laser processing notes, describing the results of the laser-material interaction for these materials, are also available in the Materials Library on the ULS website to help potential customers explore the advantages of deploying laser technology within their manufacturing, research and d