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WALTHAM, Mass.--(BUSINESS WIRE)--Deciphera Pharmaceuticals, a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, today announced that a poster presentation that includes updated results from the ongoing Phase 1 clinical study of DCC-2618, the company’s pan-KIT and PDGFRα inhibitor, will be presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting taking place June 2 - 6, 2017, in Chicago IL. Details of the presentation are as follows: Poster Title: Pharmacokinetic-driven phase 1 study of DCC-2618 a pan-KIT and PDGFR inhibitor in patients with gastrointestinal stromal tumor (GIST) and other solid tumors. Author: Filip Janku, M.D., Ph.D., The University of Texas MD Anderson Cancer Center Session: Poster Discussion Session: Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics Abstract #: 2515 Date and Time: Monday, June 5, 2017, 8:00 AM – 11:30AM (CST) Poster Discussion Session: Monday, June 5, 2017 11:30 AM-12:45 PM (CST) “We are very pleased to present these important results and to provide an update on the clinical development of DCC-2618, our pan-KIT and PDGFRα inhibitor in development for difficult to treat, KIT and/or PDGFRα-driven cancers with limited therapeutic options,” said Michael D. Taylor, Ph.D., Deciphera’s President and Chief Executive Officer. “These maturing data confirm earlier results presented at the 2016 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics,” added Oliver Rosen, M.D., Deciphera’s Chief Medical Officer. “The encouraging clinical activity achieved in patients with a broad spectrum of mutations and prior therapies in our Phase 1 study supports the impressive translational data presented last month at the 2017 American Association for Cancer Research (AACR) Annual Meeting”. About DCC-2618 DCC-2618 is currently in a first-in-human Phase 1 clinical trial. DCC-2618 is a pan-KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, glioblastoma multiforme and systemic mastocytosis. About Deciphera Pharmaceuticals Deciphera Pharmaceuticals is a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients by tackling key mechanisms of drug resistance that limit the rate and/or durability of response to existing cancer therapies. Our small molecule drug candidates are directed against an important family of enzymes called kinases, known to be directly involved in the growth and spread of many cancers. We use our deep understanding of kinase biology together with a proprietary chemistry library to purposefully design compounds that maintain kinases in a “switched off’ or inactivated conformation. These therapies comprise tumor-targeted agents designed to address therapeutic resistance causing mutations and immuno-targeted agents designed to control the activation of immunokinases that suppress critical immune system regulators, such as macrophages. We have used our platform to develop a diverse pipeline of tumor-targeted and immuno-targeted drug candidates designed to improve outcomes for patients with cancer by improving the quality, rate and/or durability of their response to treatment.


ST. HELIER, Jersey--(BUSINESS WIRE)--Novocure™ (NASDAQ:NVCR) announced today results from health-related quality of life analyses from its phase 3, pivotal EF-14 trial adding Optune to standard temozolomide chemotherapy for the treatment of newly diagnosed glioblastoma. The data, presented at this year’s World Federation of Neuro-oncology Societies 5th Quadrennial Meeting in Zurich, showed that Optune with temozolomide did not negatively impact health-related quality of life, except for itchy skin, which was most likely due to skin irritation beneath Optune’s transducer arrays. The combination treatment of Optune with temozolomide improved deterioration-free survival of several predefined health-related quality of life scales, compared to temozolomide alone, likely related to improved progression free and overall survival. “Some physicians and patients have expressed concerns regarding the possible negative impact of Optune on patient quality of life” said Eilon Kirson, M.D., Ph.D., Novocure’s Chief Science Officer and Head of Research and Development. “The health-related quality of life analyses presented this weekend show conclusively that not only was quality of life not harmed by the use of Optune with temozolomide but deterioration in quality of life was delayed compared to temozolomide alone in several health related quality of life scales, most likely due to the longer progression free and overall survival of patients treated with Optune with temozolomide.” Patients completed two validated health-related quality of life questionnaires (EORTC QLQ-C30 and BN20) at the beginning of the trial, and every three months thereafter. Health-related quality of life over time was assessed for nine preselected scales: global health, physical, cognitive, role, social and emotional functioning, itchy skin, pain and weakness of legs. The results were as follows: “This data further cements our belief that Optune plus temozolomide should be offered as an essential combination therapy to every newly diagnosed patient with glioblastoma,” said Asaf Danziger, Novocure’s CEO. “We are pleased to offer a treatment that may not only provide a survival benefit in terms of duration of life but also has the potential to provide stability or improvement in the quality of life during that time compared to the use of temozolomide alone.” Novocure is an oncology company developing a profoundly different cancer treatment centered on a proprietary therapy called TTFields, the use of electric fields tuned to specific frequencies to disrupt solid tumor cancer cell division. Novocure’s commercialized product, Optune, is approved for the treatment of adult patients with glioblastoma. Novocure has ongoing or completed clinical trials investigating TTFields in brain metastases, non-small cell lung cancer, pancreatic cancer, ovarian cancer and mesothelioma. Headquartered in Jersey, Novocure has U.S. operations in Portsmouth, New Hampshire, Malvern, Pennsylvania, and New York City. Additionally, the company has offices in Germany, Switzerland and Japan, and a research center in Israel. For additional information about the company, please visit www.novocure.com or follow us at www.twitter.com/novocure. In the United States, Optune is intended as a treatment for adult patients (22 years of age or older) with histologically-confirmed glioblastoma multiforme (GBM). In the United States, Optune with temozolomide is indicated for the treatment of adult patients with newly diagnosed, supratentorial glioblastoma following maximal debulking surgery and completion of radiation therapy together with concomitant standard of care chemotherapy. In the United States, for the treatment of recurrent GBM, Optune is indicated following histologically-or radiologically-confirmed recurrence in the supratentorial region of the brain after receiving chemotherapy. The device is intended to be used as a monotherapy, and is intended as an alternative to standard medical therapy for GBM after surgical and radiation options have been exhausted. In the European Union, Optune is intended for the treatment of patients with newly diagnosed GBM, after surgery and radiotherapy with adjuvant temozolomide, concomitant to maintenance temozolomide. The treatment is intended for adult patients, 18 years of age or older, and should be started more than 4 weeks after surgery and radiation therapy with adjuvant temozolomide. Treatment may be given together with maintenance temozolomide and after maintenance temozolomide is stopped. In the European Union, Optune is also intended for the treatment of patients with recurrent GBM who have progressed after surgery, radiotherapy and temozolomide treatment for their primary disease. The treatment is intended for adult patients, 18 years of age or older, and should be started more than 4 weeks after the latest surgery, radiation therapy or chemotherapy. Patients should only use Optune under the supervision of a physician properly trained in use of the device. Full prescribing information is available at www.optune.com/safety or by calling toll free 1-855-281-9301 in the US or by email at supportEMEA@novocure.com in the European Union. Contraindications: Do not use Optune if you have an active implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune together with implanted electronic devices has not been tested and may theoretically lead to malfunctioning of the implanted device. Use of Optune together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune ineffective. Do not use Optune if you are known to be sensitive to conductive hydrogels. In this case, skin contact with the gel used with Optune may commonly cause increased redness and itching, and rarely may even lead to severe allergic reactions such as shock and respiratory failure. Warnings and Precautions: Use Optune only after receiving training from qualified personnel, such as your doctor, a nurse, or other medical personnel who have completed a training course given by Novocure (the device manufacturer). Do not use Optune if you are pregnant, you think you might be pregnant or are trying to get pregnant. It is not known if Optune is safe or effective in these populations. The most common (≥10%) adverse events involving Optune in combination with temozolomide were low blood platelet count, nausea, constipation, vomiting, fatigue, scalp irritation from device use, headache, convulsions, and depression. The most common (≥10%) adverse events seen when using Optune alone were scalp irritation from device use and headache. The following adverse reactions were considered related to Optune when using the device alone: scalp irritation from device use, headache, malaise, muscle twitching, fall and skin ulcer. All servicing procedures must be performed by qualified and trained personnel. Do not use any parts that do not come with the Optune Treatment Kit, or that were not sent to you by the device manufacturer or given to you by your doctor. Do not wet the device or transducer arrays. If you have an underlying serious skin condition on the scalp, discuss with your doctor whether this may prevent or temporarily interfere with Optune treatment. Please see http://www.optune.com/safety to see the Optune Instructions For Use (IFU) for complete information regarding the device’s indications, contraindications, warnings, and precautions. In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Novocure’s current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, development of potential products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe” or other words and terms of similar meaning. Novocure’s performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, regulatory and political conditions as well as more specific risks and uncertainties facing Novocure such as those set forth in its Annual Report on Form 10-K filed on February 23, 2017, with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Novocure does not intend to update publicly any forward-looking statement, except as required by law. Any forward-looking statements herein speak only as of the date hereof. The Private Securities Litigation Reform Act of 1995 permits this discussion.


"Weder durch Sorafenib noch SIR-Spheres Y-90 Harz-Mikrosphären konnte ein statistisch signifikanter Vorteil hinsichtlich des Gesamtüberlebens der Studienpatienten erreicht werden," sagte Prof. Vilgrain. "Obwohl 26,6% der Patienten im SIRT-Arm per Protokoll keine SIR-Spheres erhalten haben, war der primäre Endpunkt das Gesamtüberleben in der ‚Intention-to-Treat [ITT]' Population nicht signifikant unterschiedlich (median 8,0 gegenüber 9,9 Monaten; p=0,18). Betrachtet man darüber hinaus nur diejenigen Patienten, die SIR-Spheres oder Sorafenib gemäß SARAH Protokoll erhalten haben, so war das mediane Gesamtüberleben identisch (9,9 gegenüber 9,9 Monate; p=  0,92)." Die Ergebnisse der Auswertung der Fragebögen zur Lebensqualität, welche die SARAH-Teilnehmer in dreimonatigen Abständen nach ihrer Anfangsbehandlung ausgefüllt haben, unterstreichen den Vorteil von SIR-Spheres Y-90 Harz-Mikrosphären. "Auf Basis ihrer Antworten auf Fragen zum allgemeinen Gesundheitszustand des Fragebogens der Europäischen Gesellschaft für Forschung und Behandlung von Krebs [European Organisation for Research and Treatment of Cancer - EORTC] QLQ-C30 lässt sich schließen, dass der Gesundheitszustand von Patienten, die mit SIR-Spheres behandelt wurden, während der Dauer der SARAH Studie stabil blieb, wohingegen Patienten, die mit Sorafenib behandelt wurden, von einer signifikanten und dauerhaften Verschlechterung ihres Gesundheitszustands berichteten (Gruppeneffekt: p=0,005; Zeiteffekt: p<0,001; Zunahme der Differenz zwischen den Gruppen im Laufe der Zeit: p=0,045)," sagte Prof. Vilgrain. "Für Patienten mit HCC, die weder für eine Lebertransplantation noch für chirurgische Eingriffe oder eine Ablation zur Behandlung ihrer vorhandenen Tumoren in Frage kommen, stehen die Überlebenschancen schlecht. Sie haben eine Überlebenserwartung von ein bis zwei Jahren bei zunehmender Entkräftung und Schmerzen", so Frau Prof. Vilgrain. "In vielen Fällen ist das HCC schon so weit fortgeschritten, dass Sorafenib die vorrangige Behandlungsoption darstellt. In anderen Fällen können wir Patienten im intermediären Krankheitsstadium anfänglich mit mehreren Chemotherapie-Zyklen behandeln, wobei die Infusion direkt in die Leber erfolgt, was man als transarterielle Embolisation oder TACE bezeichnet. Dieser Ansatz ist allerdings nicht immer erfolgreich." Mit 459 Patienten, die in 25 klinischen Zentren in ganz Frankreich behandelt wurden, ist SARAH die größte jemals durchgeführte randomisierte Studie zum Vergleich Selektiver Interner Radiotherapie - oder anderer zielgerichtet auf die Leber wirkender Therapien - mit systemischer Standardtherapie von primärem Leberkrebs. Fast 70% aller Patienten der SARAH Studie hatten HCC im fortgeschrittenen Stadium (Barcelona Clinic Liver Cancer Stadium C) mit Pfortaderthrombose und ohne extrahepatische Metastasen. Bei den meisten anderen Patienten hatten zwei TACE-Zyklen nicht angeschlagen. Die Ergebnisse von SIRveNIB, einer Parallelstudie mit mehr als 360 HCC-Patienten im asiatisch-pazifischen Raum, werden am 4. Juni 2017 auf der Jahrestagung der American Society of Clinical Oncology (ASCO) in Chicago vorgestellt. SIRT mit SIR-Spheres Y-90 Harz-Mikrosphären ist eine zugelassene Therapie für inoperable Lebertumoren. Es handelt sich um eine minimal-invasive Behandlungsmethode, bei der hochdosierte hochenergetische Betastrahlung direkt an die Tumoren abgegeben wird.  SIRT wird den Patienten durch Interventionelle Radiologen verabreicht, die Millionen radioaktiver Harz-Mikrosphären (Durchmesser zwischen 20 und 60 Mikrometern) über einen Katheter in die Leberarterien infundieren, über die sich die Tumoren mit Blut versorgen. Die Mikrosphären nutzen die tumoreigene Blutversorgung, um eine Strahlendosis, die 40-mal höher ist als bei einer herkömmlichen Strahlentherapie und dabei gesundes Gewebe schont, gezielt an die Lebertumoren abzugeben.


News Article | May 4, 2017
Site: www.eurekalert.org

Geneva, Switzerland, May , 2017 - Osimertinib improves cancer-related symptoms in patients with advanced lung cancer, according to an analysis of patient-reported outcomes from the AURA3 phase III clinical trial presented at the European Lung Cancer Conference (ELCC).1 "With my past experience conducting clinical trials, I often see new treatments that might be more effective, but are also usually more toxic," said lead author Dr Chee Lee, Medical Oncologist, St George Hospital Cancer Care Centre, New South Wales, Australia. "Osimertinib not only increases progression-free survival but it is well-tolerated, which makes a big difference for our patients." AURA3 included 419 patients with advanced epidermal growth factor receptor (EGFR) mutation non-small-cell lung cancer (NSCLC) who had progressed after first-line EGFR-tyrosine kinase inhibitor (TKI) therapy. They were randomised to receive the oral TKI osimertinib or chemotherapy. Patients taking osimertinib had significantly longer progression-free survival of 10.1 months versus those on chemotherapy with 4.4 months (hazard ratio 0.30; 95% confidence interval 0.23, 0.41; p Today researchers presented the findings on patient-reported outcomes from the AURA3 trial. Information was collected using two standardised European Organisation for Research and Treatment of Cancer (EORTC) questionnaires, the QLQ-LC13 that assessed lung cancer specific symptoms and the QLQ-C30 that assessed general cancer symptoms. Patients completed both questionnaires at baseline and then at regular intervals until disease progression and beyond. The researchers then analysed the findings to see if control of symptoms was better with osimertinib or chemotherapy. The researchers found that osimertinib significantly reduced many lung cancer symptoms, primarily appetite loss, fatigue, breathlessness and chest pain. There was a trend for osimertinib to reduce cough but it was not statistically significant. Dr Lee said: "It generally took longer for these symptoms to get worse in patients taking the osimertinib tablet compared to chemotherapy." In patients who had symptoms at the start of the study, appetite loss improved significantly faster on osimertinib compared to chemotherapy, and patients became less fatigued and less breathless. Compared to chemotherapy, osimertinib significantly improved global health status, physical functioning, role functioning and social functioning scores. There was a trend towards improved emotional and cognitive function with osimertinib but it was not statistically significant. "Patients taking osimertinib were more able to do normal daily activities and socialise than those on chemotherapy," said Dr Lee. He continued: "Patients with metastatic lung cancer receiving first-line treatment are really quite sick. Patients in the AURA3 trial had progressed on first-line treatment and were receiving second-line therapy, so they were even sicker. To be able to reduce cancer symptoms and improve quality of life in addition to progression-free survival for these patients is a major leap." Dr Lee concluded: "For patients with incurable cancer, prolonging only progression-free survival probably has very little meaning for them. However, treatment that can additionally improve symptoms and maintain quality of life probably means a lot for these patients." Commenting on the importance of the trial, Prof Solange Peters, Head of Medical Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland, said: "The AURA3 trial has made it clear that when patients progress on first-line targeted therapy for EGFR mutation NSCLC with a T790M resistance mutation, they should stay on targeted therapy using a new generation inhibitor rather than switching to traditional chemotherapy for the second line of therapy. Patients taking second-line osimertinib had longer progression-free survival and less toxicity than those on chemotherapy." "The data presented today shows that second-line osimertinib also significantly improved time to deterioration of important lung cancer symptoms like cough, chest pain and dyspnoea, and improved general health status," continued Peters. "Before these results clinicians had the feeling that second-line osimertinib would be efficient and better tolerated than chemotherapy but it was a subjective assumption. We now have proof that the drug has better activity, less toxicity, and improves quality of life." Regarding the need for future studies, Peters said: "Patients with EGFR mutation NSCLC should now receive frontline TKI (first or second generation) and second-line osimertinib when they have a T790M resistance mutation. We need to know if there are options other than chemotherapy for the subsequent third line of therapy." "We also have to keep in mind that osimertinib is only effective in the 55% of EGFR mutation NSCLC patients whose resistance to frontline TKI is caused by this T790M gatekeeper mutation," she continued. "More research is needed to find better second-line treatments for patients with a different mechanism of resistance, for whom chemotherapy is currently the only option. Finally, the opportunity for frontline prescription of osimertinib in all EGFR mutated NSCLC will be described by the FLAURA trial which is comparing first generation TKI to osimertinib as the very initial treatment and should report later this year." 1 Abstract 85O - 'Patient-reported symptoms and impact of treatment with osimertinib vs chemotherapy for advanced non-small-cell lung cancer, 'will be presented by Dr Chee Lee during the Proferred Paper session 'Immunotherapies and targeted therapies in advanced NSCLC' on Saturday, 6 May, 14:45 (CEST). 2 Mok TS, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017;376(7):629-640. doi: 10.1056/NEJMoa1612674. This press release contains information provided by the authors of the highlighted abstracts and reflects the content of those abstracts. It does not necessarily reflect the views or opinions of ESMO or IASLC who cannot be held responsible for the accuracy of the data. Commentators quoted in the press release are required to comply with the ESMO Declaration of Interests policy and the ESMO Code of Conduct. The European Lung Cancer Conference (ELCC) is the reference event in Europe for professionals treating lung cancers. It is organised by the European Society for Medical Oncology and the International Association for the Study of Lung Cancer in partnership with ESTRO and ETOP. ELCC provides a comprehensive multidisciplinary overview of the latest as well as of the state-of-the-art knowledge in thoracic malignancies, covering different aspects such as prevention, screening, diagnosis, treatment modalities and the results of basic, clinical and translational research, presented by top international academic experts. Around 2,000 attendees are expected from throughout Europe and the rest of the world. About the European Society for Medical Oncology (ESMO) ESMO is the leading professional organisation for medical oncology. With more than 15,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment. http://www. About the International Association for the Study of Lung Cancer (IASLC) The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association's membership includes more than 5,000 lung cancer specialists in over 100 countries. Visit http://www. for more information.


La différence en matière de fréquence et de sévérité des effets secondaires chez les patients traités par les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 comparé au sorafenib est marquante. Un nombre significativement plus faible de patients traités par les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 a souffert d'effets secondaires liés au traitement en général (76,5 % vs. 94,0 % pour le sorafenib ; p<0.001), et ceux-ci étaient également moins sévères (≥ grade 3 ; 40,7 % vs. 63,0 %, respectivement ; p<0,001). En outre, parmi les patients traités par les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 qui ont fait état d'effets secondaires liés au traitement, la médiane d'occurrence est de seulement 5 tout au long de l'étude SARAH contre 10 pour ceux traités par sorafenib (p<0,001). Les symptômes généraux liés au traitement tels que la fatigue (42 % vs. 65 % ; p<0,001), les douleurs abdominales (20 % vs. 29 % ; p=0,032), les nausées ou vomissements (12 % vs. 23 % ; p=0,001) et les infections (4 % vs. 11 % ; p=0,007) ont également été significativement moins souvent rapportés et moins sévères pour les patients traités par les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 que pour les patients traités par sorafenib. Moins de patients traités par les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 ont souffert de diarrhées (13 % vs. 68 % pour le sorafenib ; p<0,001), de syndrome main-pied (0,4 % vs. 21 % ; p<0,001), d'anorexie (13 % vs. 32 % ; p<0,001), de perte de poids (6 % vs. 21 % ; p<0,001) et d'alopécie (0 % vs. 16 % ; p<0,001), ainsi que d'infections (4 % vs. 11 % ; p=0,007), d'hypertension (3 % vs. 13 % ; p<0,001) et d'hémorragies gastro-intestinales (3 % vs. 10 % ; p=0,002). Il y a eu peu de complications associées au traitement SIRT et, plus important encore, aucune maladie du foie liée à la radioembolisation (hépatite radique). Les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 n'ont pas entrainé d'augmentation significative des ulcérations gastro-intestinales (GI) (2 % vs. 0,5 % pour le sorafenib ; p=0,37) incluant un cas d'ulcère GI provoqué par les radiations, d'ascites (12 % vs. 11 % ; p=0,57), d'hyperbilirubinémie (12 % vs. 13 % ; p=0,86) et seulement un cas de pneumonie post-radiation (0,4 % vs. 0 ; p=0,46). Les résultats des enquêtes sur la qualité de vie remplies par les participants tous les trois mois après le premier traitement mettent en valeur les bénéfices des microsphères SIR-Spheres en résine marquées à l'Yttrium 90. « Sur la base de leurs réponses aux questions sur l'état de santé général du questionnaire QLQ-C30 de l'European Organisation for Research and Treatment of Cancer [EORTC], les patients traités par SIR-Spheres ont présenté un état de santé stable tout au long de l'étude SARAH, tandis que les patients traités au sorafenib ont fait état d'un déclin constant et significatif de leur qualité de vie (effet de groupe : p=0,005 ; effet sur la durée : p<0,001 ; différence entre les groupes sur la durée : p=0,045) » a déclaré le Prof. Vilgrain. « En outre, » a-t-elle souligné, « nous avons découvert que les tumeurs des patients traités par SIR-Spheres présentaient une meilleure réponse objective (19,0 % vs. 11,6 % ; p=0.042) que celles des patients traités au sorafenib, et représentaient un risque significativement moindre de progression du cancer dans le foie, ce qui est la principale cause de décès lié à cette maladie. » « Pour les patients atteints de CHC avancé ou ceux pour qui la TACE a échoué, nous nous appuyons depuis une dizaine d'années sur le traitement systémique par voie orale au sorafenib, qui a été démontré plus efficace que le placebo en termes de survie, mais qui cause également de nombreux effets secondaires qui peuvent avoir un impact négatif sur la qualité de vie des patients. C'est pourquoi nous avons décidé de regarder si une nouvelle forme de thérapie ciblant le foie, la radiothérapie interne sélective, ou SIRT, avec SIR-Spheres pourrait représenter une meilleure alternative. Notre décision de mettre en œuvre l'étude SARAH est basée sur de plus petites études existantes et des analyses rétrospectives, qui suggèrent que les SIR-Spheres pourraient être au moins aussi efficaces et aussi bien tolérées par les patients atteints de CHC. » a-t-elle ajouté. Avec 459 patients traités dans 25 centres cliniques français, SARAH est la plus grande étude randomisée à ce jour à comparer la radiothérapie interne sélective - ou toute autre thérapie ciblant le foie - avec la thérapie systémique standard pour le traitement du cancer primitif du foie. Près de 70 % des patients de l'étude SARAH souffraient d'un CHC avancé (Barcelona Clinic Liver Cancer (BCLC) stade C), avec thrombose de la veine porte et sans propagation extra-hépatique. La plupart des autres patients avaient été soumis à deux cycles de TACE ayant échoué. Les patients atteints de CHC représentent 90 % de toutes les personnes souffrant de cancer primitif du foie, la sixième forme de cancer la plus fréquente dans le monde et la seconde cause de décès liée au cancer. Le CHC affecte principalement les patients atteints de cirrhose, toutes causes confondues, y compris l'hépatite virale, l'alcoolisme et la maladie du foie gras, et est la cause de plus de 670 000 décès par an dans le monde.2 Pour les personnes à risque, l'incidence du CHC augmente progressivement avec l'âge pour atteindre un pic autour de 70 ans.3 En plus de ces causes, on estime désormais que jusqu'à un patient sur huit (12,8 %) atteint de stéatohépatite non-alcoolique (NASH) avec cirrhose évoluera vers un CHC.7 La NASH, qui est largement considérée comme déclenchée par le diabète de type II, la résistance à l'insuline, l'obésité, l'hyperlipidémie et l'hypertension, est devenue la première cause de maladie hépatique dans les pays occidentaux. La progression de la NASH augmente dramatiquement les risques de cirrhose, d'insuffisance hépatique et de CHC. On pense que cette évolution est liée à l'épidémie mondiale de diabète et d'obésité.8 Les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 sont approuvées pour le traitement des tumeurs du foie inopérables en Argentine, en Australie, au Brésil, dans l'Union européenne (marquage CE), en Suisse, en Turquie et plusieurs pays d'Asie. Aux États-Unis, les microsphères SIR-Spheres en résine marquées à l'Yttrium 90 bénéficient d'une homologation de pré-commercialisation (PMA) de la FDA, et sont indiquées pour le traitement de métastases hépatiques non résécables issues d'un cancer primitif colorectal, en combinaison avec une chimiothérapie intra-artérielle hépatique utilisant de la floxuridine (FUDR). Références: 1. Vilgrain V et al.  The International Liver Congress™ 2017 – 52nd annual meeting of the European Association for the Study of the Liver, J Hepatol 2017; 66 (Suppl 1): Abs. GS-012. 2. Extrapolated from Ferlay J et al.  Globocan 2012. v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr, accessed on 14/April/2017.


The results, which could impact the treatment of tens of thousands of liver cancer patients annually, were announced by the principal investigator of the SARAH study, Professor Valérie Vilgrain MD, PhD, Department of Radiology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP) and Université Paris Diderot, Sorbonne Paris Cité, France. "Neither sorafenib nor SIR-Spheres Y-90 resin microspheres produced a statistically significant difference in Overall Survival (OS) of the patients we studied," said Prof. Vilgrain.  "Despite 26.6% of patients in the SIRT arm not receiving SIR-Spheres per protocol, the primary endpoint of Overall Survival by intention-to-treat [ITT] was not significantly different (median 8.0 vs. 9.9 months; p=0.18). Moreover, if we look at the patients who received SIR-Spheres or sorafenib according to the SARAH protocol, median OS was identical (9.9 vs. 9.9 months; p=0.92)." "In terms of what matters for patients, the findings from this first large head-to-head comparison of liver-directed Selective Internal Radiation Therapy (SIRT) and systemic chemotherapy with sorafenib also show clearly that liver-directed procedures with SIR-Spheres result in a significantly better tolerance of treatment and quality of life," Prof. Vilgrain stated.  "I believe this consideration should be a critical factor in selecting first-line treatment for this patient population in the future." The difference in the frequency and severity of side effects of patients treated with SIR-Spheres Y-90 resin microspheres versus sorafenib was striking. Significantly fewer patients treated with SIR-Spheres Y-90 resin microspheres had any treatment-related side effects at all (76.5% vs. 94.0% for sorafenib; p<0.001), and these were also less severe (≥ grade 3; 40.7% vs. 63.0%, respectively; p<0.001). Moreover, those patients treated with SIR-Spheres Y-90 resin microspheres who reported treatment-related side effects experienced a median of only 5 such events over the course of the SARAH study, compared to a median of 10 events in those who received sorafenib (p<0.001). General treatment-related symptoms such as fatigue (42% vs. 65%; p<0.001), abdominal pain (20% vs. 29%; p=0.032), nausea or vomiting (12% vs. 23%; p=0.001) and infection (4% vs. 11%; p=0.007) were also significantly less frequently reported and less severe for patients receiving SIR-Spheres Y-90 resin microspheres, compared to sorafenib. Fewer patients receiving SIR-Spheres Y-90 resin microspheres experienced treatment-related diarrhoea (13% vs. 68% for sorafenib; p<0.001), hand-foot skin reaction (0.4% vs. 21%; p<0.001), anorexia (13% vs. 32%; p<0.001), weight loss (6% vs. 21%; p<0.001) and alopecia (0% vs. 16%; p<0.001), as well as infections (4% vs. 11%; p=0.007), hypertension (3% vs. 13%; p<0.001) and non-gastrointestinal haemorrhage (3% vs. 10%; p=0.002). There were few potential SIRT-associated treatment-related complications and, importantly, no radioembolization-induced liver disease (radiation hepatitis) experienced. There were no significant increases for SIR-Spheres Y-90 resin microspheres in gastrointestinal (GI) ulceration (2% vs. 0.5% for sorafenib; p=0.37) including one case of radiation-induced GI ulcer, ascites (12% vs. 11%; p=0.57), hyperbilirubinemia (12% vs. 13%; p=0.86) and only one case of radiation pneumonitis (0.4% vs. 0; p=0.46). The results of Quality of Life (QoL) surveys filled out by SARAH participants at three month intervals after their initial treatment underscored the benefit of SIR-Spheres Y-90 resin microspheres. "Based on their responses to the Global Health Status questions in the European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 questionnaire, patients treated with SIR-Spheres maintained their health status over the duration of the SARAH study, whereas patients receiving sorafenib reported a significant and sustained decline in QoL (group effect: p=0.005; time effect: p<0.001; between group difference increase over time: p=0.045)," Prof. Vilgrain said. "In addition," she noted, "we found that the tumours of patients treated with SIR-Spheres had a higher objective response (19.0% vs. 11.6%; p=0.042) than was seen with sorafenib, and experienced a significantly reduced risk of their cancer progressing in the liver, which is the main cause of death from this disease." "Patients with HCC who are not eligible for liver transplant, surgery or ablation to treat their tumours in place face a very bleak prognosis of one or two years of life with increasing debilitation and pain," Prof. Vilgrain said.  "In many cases, the patient's HCC is already so advanced that the main treatment option available is sorafenib. In other cases, we are able to treat patients with intermediate-stage disease initially with several courses of chemotherapy infused directly into their livers, which is called transarterial chemoembolisation, or TACE, but this approach may fail." "For patients with advanced HCC or those failing TACE, we have for the past ten years relied upon oral systemic treatment with sorafenib, which was shown to extend survival compared to placebo, but also causes many side effects that can compromise patients' quality of life.  That is why we decided to see if treatment with a newer form of liver-directed therapy, selective internal radiotherapy, or SIRT, with SIR-Spheres could represent a better alternative.  Our decision to initiate the SARAH study was based on smaller previous studies and retrospective analyses, which suggested that SIR-Spheres could be at least as effective and was well tolerated by HCC patients," she stated. The randomized, controlled, open-labelled SARAH ( or fenib versus adioembolization in dvanced epatocellular carcinoma) study directly compared the efficacy of selective internal radiation therapy (SIRT, or radioembolisation) using yttrium-90 [Y-90] resin microspheres (SIR-Spheres Y-90 resin microspheres, Sirtex Medical Limited, Sydney, Australia) versus sorafenib (Nexavar®, Bayer HealthCare Pharmaceuticals, Berlin, Germany). SARAH was launched in December 2011 and concluded enrolment in February 2015. With 459 patients treated in 25 clinical centres across France, SARAH is the largest randomized study ever to compare selective internal radiation therapy - or any liver-directed therapy - against the standard-of-care systemic therapy in the treatment of primary liver cancer.  Almost 70% of the patients in the SARAH study had advanced HCC (Barcelona Clinic Liver Cancer stage C), with portal vein thrombosis and no extrahepatic spread. Most of the other patients had failed two cycles of TACE. Results of SIRveNIB, a parallel study in more than 360 Asia Pacific HCC patients will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on 4 June 2017. HCC patients represent 90% of all people diagnosed with primary liver cancer, which is the sixth most common cancer in the world and the second leading cause of cancer-related death.  HCC affects mainly patients with cirrhosis from any cause, including viral hepatitis, alcohol misuse, and fatty liver disease, and results in more than 670,000 deaths globally each year.[2] Among people at risk of HCC, incidence of the disease increases progressively with advancing age, reaching a peak at around 70 years.[3] Overall, one-third of patients with liver cirrhosis will develop HCC during their lifetime.[4] In addition to these causes, it is now thought that up to one in eight (12.8%) of non-alcoholic steatohepatitis (NASH) patients with cirrhosis will progress to HCC.[7] NASH - which is widely considered to be triggered by type II diabetes, insulin resistance, obesity, hyperlipidaemia and hypertension - has become the number one cause of liver disease in Western countries.  Progression of NASH dramatically increases the risks of cirrhosis, liver failure, and HCC.  This is thought to be related to the worldwide epidemic of diabetes and obesity.[8] HCC occurs more often in men than women, except in Africa, where more women are affected.[2] What is SIRT with SIR-Spheres Y-90 resin microspheres? SIRT with SIR-Spheres Y-90 resin microspheres is an approved treatment for inoperable liver tumours. It is a minimally-invasive treatment that delivers high doses of high-energy beta radiation directly to the tumours.  SIRT is administered to patients by interventional radiologists, who infuse millions of radioactive resin microspheres (diameter between 20-60 microns) via a catheter into the liver arteries that supply blood to the tumours. By using the tumours' blood supply, the microspheres selectively target liver tumours with a dose of radiation that is up to 40 times higher than conventional radiotherapy, while sparing healthy tissue. SIR-Spheres Y-90 resin microspheres are approved for use in Argentina, Australia, Brazil, the European Union (CE Mark), Switzerland, Turkey, and several countries in Asia for the treatment of unresectable liver tumours. In the US, SIR-Spheres Y-90 resin microspheres have a Pre-Market Approval (PMA) from the FDA and are indicated for the treatment of unresectable metastatic liver tumours from primary colorectal cancer with adjuvant intra-hepatic artery chemotherapy (IHAC) of FUDR (floxuridine). SIR-Spheres® is a Registered Trademark of Sirtex SIR-Spheres Pty Ltd.


The results, which could impact the treatment of tens of thousands of liver cancer patients annually, were announced by the principal investigator of the SARAH study, Professor Valérie Vilgrain MD, PhD, Department of Radiology, Beaujon Hospital, Assistance Publique - Hôpitaux de Paris (AP-HP) and Université Paris Diderot, Sorbonne Paris Cité, France. "Neither sorafenib nor SIR-Spheres Y-90 resin microspheres produced a statistically significant difference in Overall Survival (OS) of the patients we studied," said Prof. Vilgrain.  "Despite 26.6% of patients in the SIRT arm not receiving SIR-Spheres per protocol, the primary endpoint of Overall Survival by intention-to-treat [ITT] was not significantly different (median 8.0 vs. 9.9 months; p=0.18). Moreover, if we look at the patients who received SIR-Spheres or sorafenib according to the SARAH protocol, median OS was identical (9.9 vs. 9.9 months; p=0.92)." "In terms of what matters for patients, the findings from this first large head-to-head comparison of liver-directed Selective Internal Radiation Therapy (SIRT) and systemic chemotherapy with sorafenib also show clearly that liver-directed procedures with SIR-Spheres result in a significantly better tolerance of treatment and quality of life," Prof. Vilgrain stated.  "I believe this consideration should be a critical factor in selecting first-line treatment for this patient population in the future." The difference in the frequency and severity of side effects of patients treated with SIR-Spheres Y-90 resin microspheres versus sorafenib was striking. Significantly fewer patients treated with SIR-Spheres Y-90 resin microspheres had any treatment-related side effects at all (76.5% vs. 94.0% for sorafenib; p<0.001), and these were also less severe (≥ grade 3; 40.7% vs. 63.0%, respectively; p<0.001). Moreover, those patients treated with SIR-Spheres Y-90 resin microspheres who reported treatment-related side effects experienced a median of only 5 such events over the course of the SARAH study, compared to a median of 10 events in those who received sorafenib (p<0.001). General treatment-related symptoms such as fatigue (42% vs. 65%; p<0.001), abdominal pain (20% vs. 29%; p=0.032), nausea or vomiting (12% vs. 23%; p=0.001) and infection (4% vs. 11%; p=0.007) were also significantly less frequently reported and less severe for patients receiving SIR-Spheres Y-90 resin microspheres, compared to sorafenib. Fewer patients receiving SIR-Spheres Y-90 resin microspheres experienced treatment-related diarrhoea (13% vs. 68% for sorafenib; p<0.001), hand-foot skin reaction (0.4% vs. 21%; p<0.001), anorexia (13% vs. 32%; p<0.001), weight loss (6% vs. 21%; p<0.001) and alopecia (0% vs. 16%; p<0.001), as well as infections (4% vs. 11%; p=0.007), hypertension (3% vs. 13%; p<0.001) and non-gastrointestinal haemorrhage (3% vs. 10%; p=0.002). There were few potential SIRT-associated treatment-related complications and, importantly, no radioembolization-induced liver disease (radiation hepatitis) experienced. There were no significant increases for SIR-Spheres Y-90 resin microspheres in gastrointestinal (GI) ulceration (2% vs. 0.5% for sorafenib; p=0.37) including one case of radiation-induced GI ulcer, ascites (12% vs. 11%; p=0.57), hyperbilirubinemia (12% vs. 13%; p=0.86) and only one case of radiation pneumonitis (0.4% vs. 0; p=0.46). The results of Quality of Life (QoL) surveys filled out by SARAH participants at three month intervals after their initial treatment underscored the benefit of SIR-Spheres Y-90 resin microspheres. "Based on their responses to the Global Health Status questions in the European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 questionnaire, patients treated with SIR-Spheres maintained their health status over the duration of the SARAH study, whereas patients receiving sorafenib reported a significant and sustained decline in QoL (group effect: p=0.005; time effect: p<0.001; between group difference increase over time: p=0.045)," Prof. Vilgrain said. "In addition," she noted, "we found that the tumours of patients treated with SIR-Spheres had a higher objective response (19.0% vs. 11.6%; p=0.042) than was seen with sorafenib, and experienced a significantly reduced risk of their cancer progressing in the liver, which is the main cause of death from this disease." "Patients with HCC who are not eligible for liver transplant, surgery or ablation to treat their tumours in place face a very bleak prognosis of one or two years of life with increasing debilitation and pain," Prof. Vilgrain said.  "In many cases, the patient's HCC is already so advanced that the main treatment option available is sorafenib. In other cases, we are able to treat patients with intermediate-stage disease initially with several courses of chemotherapy infused directly into their livers, which is called transarterial chemoembolisation, or TACE, but this approach may fail." "For patients with advanced HCC or those failing TACE, we have for the past ten years relied upon oral systemic treatment with sorafenib, which was shown to extend survival compared to placebo, but also causes many side effects that can compromise patients' quality of life.  That is why we decided to see if treatment with a newer form of liver-directed therapy, selective internal radiotherapy, or SIRT, with SIR-Spheres could represent a better alternative.  Our decision to initiate the SARAH study was based on smaller previous studies and retrospective analyses, which suggested that SIR-Spheres could be at least as effective and was well tolerated by HCC patients," she stated. The randomized, controlled, open-labelled SARAH ( or fenib versus adioembolization in dvanced epatocellular carcinoma) study directly compared the efficacy of selective internal radiation therapy (SIRT, or radioembolisation) using yttrium-90 [Y-90] resin microspheres (SIR-Spheres Y-90 resin microspheres, Sirtex Medical Limited, Sydney, Australia) versus sorafenib (Nexavar®, Bayer HealthCare Pharmaceuticals, Berlin, Germany). SARAH was launched in December 2011 and concluded enrolment in February 2015. With 459 patients treated in 25 clinical centres across France, SARAH is the largest randomized study ever to compare selective internal radiation therapy - or any liver-directed therapy - against the standard-of-care systemic therapy in the treatment of primary liver cancer.  Almost 70% of the patients in the SARAH study had advanced HCC (Barcelona Clinic Liver Cancer stage C), with portal vein thrombosis and no extrahepatic spread. Most of the other patients had failed two cycles of TACE. Results of SIRveNIB, a parallel study in more than 360 Asia Pacific HCC patients will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on 4 June 2017. HCC patients represent 90% of all people diagnosed with primary liver cancer, which is the sixth most common cancer in the world and the second leading cause of cancer-related death.  HCC affects mainly patients with cirrhosis from any cause, including viral hepatitis, alcohol misuse, and fatty liver disease, and results in more than 670,000 deaths globally each year.[2] Among people at risk of HCC, incidence of the disease increases progressively with advancing age, reaching a peak at around 70 years.[3] Overall, one-third of patients with liver cirrhosis will develop HCC during their lifetime.[4] In addition to these causes, it is now thought that up to one in eight (12.8%) of non-alcoholic steatohepatitis (NASH) patients with cirrhosis will progress to HCC.[7] NASH - which is widely considered to be triggered by type II diabetes, insulin resistance, obesity, hyperlipidaemia and hypertension - has become the number one cause of liver disease in Western countries.  Progression of NASH dramatically increases the risks of cirrhosis, liver failure, and HCC.  This is thought to be related to the worldwide epidemic of diabetes and obesity.[8] HCC occurs more often in men than women, except in Africa, where more women are affected.[2] What is SIRT with SIR-Spheres Y-90 resin microspheres? SIRT with SIR-Spheres Y-90 resin microspheres is an approved treatment for inoperable liver tumours. It is a minimally-invasive treatment that delivers high doses of high-energy beta radiation directly to the tumours.  SIRT is administered to patients by interventional radiologists, who infuse millions of radioactive resin microspheres (diameter between 20-60 microns) via a catheter into the liver arteries that supply blood to the tumours. By using the tumours' blood supply, the microspheres selectively target liver tumours with a dose of radiation that is up to 40 times higher than conventional radiotherapy, while sparing healthy tissue. SIR-Spheres Y-90 resin microspheres are approved for use in Argentina, Australia, Brazil, the European Union (CE Mark), Switzerland, Turkey, and several countries in Asia for the treatment of unresectable liver tumours. In the US, SIR-Spheres Y-90 resin microspheres have a Pre-Market Approval (PMA) from the FDA and are indicated for the treatment of unresectable metastatic liver tumours from primary colorectal cancer with adjuvant intra-hepatic artery chemotherapy (IHAC) of FUDR (floxuridine). SIR-Spheres® is a Registered Trademark of Sirtex SIR-Spheres Pty Ltd.


News Article | August 2, 2017
Site: www.eurekalert.org

Lugano/Brussels, Aug. 3, 2017. Three leading European organisations in the fight against cancer have called the EU to urgently increase its support for independent academic research for the benefit of cancer patients, in an article published (today) in ESMO Open (1). "Independent academic research is endangered for lack of funds and adequate legislation," said Rolf A. Stahel, ESMO Past President and co-founder of the CAREFOR platform. "Working closely with EU institutions, we can make sure Europe is equipped with efficient legal framework and a vision to become the best place for research and innovation, for the ultimate benefit of cancer patients," he stated. CAREFOR (the Clinical Academic Cancer Research Forum) is a joint initiative by the European Association for Cancer Research (EACR), the European Organisation for the Research and Treatment of Cancer (EORTC), and the European Society for Medical Oncology (ESMO). In this paper, they address the funding and regulatory challenges faced by academic researchers, as well as the need to foster collaborative cancer research by developing novel approaches to clinical trials. How can we benefit from non-commercial clinical research? The CAREFOR paper explains that the three main areas that would benefit from academic research are: personalised medicine, patient-centred innovation and rare cancer patients. "Cancer is a complex disease that continuously evolves under treatment. New discoveries have revealed that there are an enormous number of cancer subtypes, which each present unique characteristics. A combination of basic and clinical research will play an increasingly important role in the development of tailored treatment options leading to improved therapeutic strategies," explains Richard Marais, EACR Past President. "With 3.2 million new cases of cancer per year and considering the increasing number of patients with rare conditions, non-commercial research is essential as it has the potential to optimise therapeutic strategies for frequent tumours and address the unmet needs of rare cancer patients through the use of new methodologies for evidence generation and evaluation. Independent researchers address pragmatic questions critically relevant to treat patients in real life, including -- but not limited to -- combination of treatments and treatment duration, thus taking into account medical value and clinical relevance of treatments," explains Denis Lacombe, EORTC Director General. The CAREFOR paper states that independent collaborative research platforms are in the best position to optimise knowledge development. This approach would help to switch from a traditional drug-centered research and approval process to a truly patient-centered approach. "The aim is to find the trial that fits the patient, rather than finding the patient fit for the trial," said Stahel. "To achieve this, it is fundamental that existing challenges faced by independent academic researchers are solved." "Key issues that we are calling EU institutions to address include: appropriate implementation of the Clinical Trials and Data Protection Regulations; the need for funding for independent research; and the need to foster academic collaborative environments," explained Stahel. "We are also calling for a common EU database to track all clinical trials in Europe." Other critical issues addressed in the CAREFOR paper include: the affordability of cancer care; the need for independent, collaborative and quality biobanks; the acceptance of new methodologies for evidence generation and evaluation, and the use and protection of electronic patient data. "The bottom line is that academic and independent research helps to save time, lower costs, accelerate commercial drug development and improve access for patients," concludes Stahel. ESMO Open is the European Society for Medical Oncology's open access, peer-reviewed, online-only journal, dedicated to publishing high-quality medical research and educational content from all disciplines of oncology, with a focus on innovative clinical and translational cancer research. CAREFOR has a mission to improve the situation for academic clinical trials in the field of oncology in Europe. CAREFOR will The goal of CAREFOR is to institutionalize academic cancer clinical research in the European landscape. Powered by: EACR, EORTC, ESMO and joined by: European and International groups, umbrella organizations, societies, national groups, numerous cancer centres and non-European guests. ESMO is the leading professional organisation for medical oncology. With 16,000 members representing oncology professionals from over 130 countries worldwide, ESMO is the society of reference for oncology education and information. We are committed to supporting our members to develop and advance in a fast-evolving professional environment. The European Organisation for the Research and Treatment of Cancer (EORTC) unites cancer clinical research experts to define better treatments for cancer patients to prolong survival and improve quality of life. Both international and multidisciplinary, EORTC's Network comprises over 4600 collaborators involved in cancer treatment and research in more than 800 hospitals across 35 countries. The EACR is Europe's professional membership association for those working and studying in cancer research, with over 10,000 members worldwide. Our mission is "The advancement of cancer research for the public benefit: from basic research to prevention, treatment and care."

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