Onco Actu du 8 décembre 2015

	1. Biologie
Loss of enzyme promotes tumor progression in endometrial cancer [MD Anderson Cancer Center] CD73 is the crucial enzyme for generating adenosine, a signaling molecule important for regulation of normal tissue function and stability or homeostasis.
Genetic mutations differ within a single tumor, study finds [University of Michigan Health System] When researchers looked at different areas within an individual rectal cancer sample, they found cases in which each area contained different genetic mutations. The findings could have significant implications for treatment recommendations.
	2.11 Etiologie - Alimentation
Japan: Ham-giving tradition hit by WHO cancer report [BBC News] Hams are among items traditionally sent during the oseibo gift-giving season in December, but the WHO's report linking processed meats with bowel cancer mean that sales are lower than in previous years, The Japan Times newspaper says.
	2.6 Etiologie - Environnement
Scientists assembled for Monsanto say herbicide not carcinogenic, disputing WHO report [Reuters] The group said that the WHO's International Agency for Research on Cancer (IARC) misinterpreted or incorrectly weighted some of the data it reviewed and ignored other data before classifying glyphosate as a probable human carcinogen, according to an abstract of its findings.
	3.1 Tabac
E-cigarette flavorings have dangerous chemicals [STAT] The Environmental Health Perspectives, a journal published by the National Institute of Environmental Health Sciences, says that some companies hide the presence of the flavoring chemical, known as diacetyl, as well as other potentially harmful artificial flavorings.
E-cigarettes contain flavouring chemical linked to deadly 'popcorn lung' [The Telegraph] "Since most of the health concerns about e-cigarettes have focused on nicotine, there is still much we do not know about e-cigarettes” said study co-author Dr David Christiani, Professor of Environmental Genetics. “In addition to containing varying levels of the addictive substance nicotine, they also contain other cancer-causing chemicals, such as formaldehyde, and as our study shows, flavouring chemicals that can cause lung damage.”
	5. Traitements
A dive into patient records uncovers possible connection between cancer treatment, Alzheimer’s [Scope Blog] Among a group of about 17,000 prostate cancer patients, those treated with a medication that suppresses testosterone — so-called androgen blockers — had nearly twice the overall rate of later developing Alzheimer’s disease.
A new way to deliver microRNAs for cancer treatment [MIT News] Scientists exploit gene therapy to shrink tumors in mice with an aggressive form of breast cancer.
	5.12 Immunothérapies
Novartis says CART study findings bolster 2017 approval case [Reuters] The findings show 93 percent initially had complete remission, Novartis said, while 55 percent had remission-free survival at 12 months. After 12 months, 18 patients had ongoing complete remission.
With SQZ Deal, Roche Finally Dips Its Toes into Cell Therapy [Xconomy] SQZ has made a chip that can be used to sort cells, one by one, and insert material into cells without killing them. Roche and SQZ want to take antigens from a patient’s tumor, insert them into the patient’s B cells—all done outside the body—then give the “stuffed” B cells back to the patient. The theory is that the modified B cells would train the body’s T cells to hunt down the cancer.
	5.2 Pharma
ARIAD Announces Initiation of OPTIC-2L Randomized Phase 3 Trial of ponatinib vs. nilotinib in Second-Line Patients with Chronic-Phase Chronic Myeloid Leukemia [ARIAD Pharmaceuticals] This study is designed to demonstrate superiority of ponatinib over nilotinib and will enroll patients with CP-CML who have become resistant to imatinib and have received no other tyrosine kinase inhibitor.
Threshold Goes Under the Threshold [In the Pipeline] Threshold’s idea was not a bad one at all. It just didn’t work, for reasons that are not clear. A lot of clinical results are not clear – even the good results aren’t always good for the reasons that people were expecting.
	5.2.1 Pharma - Partenariats
Celgene in Collaboration with Astrazeneca Announce Initiation of Fusion Clinical Development Program in Immuno-Oncology [Celgene] Program starting with four studies of durvalumab and combination therapies across multiple hematologic disorders.
	5.3 Traitements - FDA, EMA,...
UK Patients With NSCLC to get Early Access to Tagrisso [RAPS] Tagrisso (osimertinib) is currently being reviewed by the European Medicines Agency (EMA), and was granted Breakthrough Therapy designation in the US before being approved by the Food and Drug Administration (FDA) in November.
	5.8.2 ASH - Pharma
Seattle Genetics Highlights ADCETRIS® (Brentuximab Vedotin) Data Presentations in Frontline Non-Hodgkin Lymphoma at ASH 2015 [Seattle Genetics] The data include an oral presentation highlighting updated results from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with chemotherapy for newly diagnosed, high risk diffuse large B-cell lymphoma (DLBCL) patients.
Seattle Genetics Demonstrates Commitment to Improve Hodgkin Lymphoma (HL) Treatment Paradigm Through Multiple ADCETRIS® (Brentuximab Vedotin) Data Presentations at ASH 2015 [Seattle Genetics] Final Pivotal Trial Results in Relapsed/Refractory HL Demonstrate Durable Remissions Lasting More than Five Years After ADCETRIS Monotherapy.
Seattle Genetics Highlights Vadastuximab Talirine (SGN-CD33A) Data Presentations in Patients with Acute Myeloid Leukemia at ASH 2015 [Seattle Genetics] 33A Combination Therapy and Monotherapy Demonstrate Encouraging Anti-leukemic Activity in AML; Data Highlighted in Oral Presentations.
RATIFYing a novel agent in the treatment of AML: Midostaurin shows efficacy in front-line therapy [The OBR Blog] Midostaurin will be unchallenged initially in newly diagnosed FLT3+ patients, but should any of these competitors move into first-line testing they could pose a direct threat to midostaurin.
Novartis drug PKC412 (midostaurin) improves overall survival by 23% in global Phase III study of AML patients with FLT3 mutations [Novartis] he trial evaluated the addition of either PKC412 (midostaurin) or placebo to daunorubicin/cytarabine in the induction phase, followed by high-dose cytarabine in the consolidation phase; patients who achieved complete remission after consolidation chemotherapy continued treatment with PKC412 (midostaurin) or placebo as a single agent for up to one year.
Combination Ibrutinib (IMBRUVICA®) Demonstrates a Strong Response Rate in Treatment-Naive Patients with Follicular Lymphoma [AbbVie] The multicenter, open-label Phase 2 study evaluated the safety and efficacy of ibrutinib plus rituximab in 60 treatment-naive patients with histologically confirmed FL.
First Data Unveiled from CALLISTO Program Examining the Use of XARELTO® (rivaroxaban) for Treating Blood Clots in People with Cancer [Johnson & Johnson] The study, funded by Janssen and conducted at Memorial Sloan Kettering Cancer Center, followed 200 patients with cancer who were diagnosed with VTE and treated with rivaroxaban for six months.
Phase III data shows Sandoz' proposed biosimilar pegfilgrastim has similar safety and efficacy as the reference product [Novartis] The PROTECT 2 study was a global, randomized, double-blind trial involving 308 patients carried out in the United States, Latin America, Asia and Europe. The safety and immunogenicity of the proposed biosimilar was assessed for four weeks after the final study drug administration. The study analyzed the duration of severe neutropenia (DSN), which was also the primary endpoint.
IMBRUVICA® (Ibrutinib) Phase 3 RAY Data Show Significant Reductions in Disease Progression versus Temsirolimus in Relapsed/Refractory Mantle Cell Lymphoma Patients [AbbVie] MBRUVICA significantly improved PFS as determined by an Independent Review Committee (IRC) compared to treatment with temsirolimus, resulting in a reduction in the risk of disease progression or death by 57% after a median follow-up of 20 months.
	5.8.3 ASH - Divers
Penn Study: Mutations in Chronic Lymphocytic Leukemia Suggest Potential New Uses of Existing Cancer Drugs [Penn Medicine] The team used next generation sequencing to take a deeper dive into 87 CLL patients’ genetic makeup. They captured a slew of mutations known to be associated with other cancers: ATM, TP53, BRAF and KRAS, to name a few.
	5.8.4 ASH - CAR T
Juno’s Investigational CAR T Cell Product Candidates JCAR015 and JCAR014 Demonstrate Encouraging Clinical Responses in Patients with B-cell Cancers [Juno Therapeutics] “The JCAR014 data presented show the addition of fludarabine to cyclophosphamide-based lymphodepletion improves CAR T cell expansion, persistence, and disease-free survival in r/r B-cell adult ALL patients treated with a defined cell product. The continued translational insights from this ongoing trial also demonstrate the importance of depth of response in order to maintain a durable response.”
Novartis announces new CTL019 study data demonstrating overall response in adult patients with certain types of lymphoma [Novartis] The study findings include 26 adult patients (15 with DLBCL and 11 with FL) who were evaluable for response. The study found that three patients with DLBCL who achieved a partial response (PR) to treatment at three months converted to complete response (CR) by six months.
Novartis highlights new CTL019 Phase II data demonstrating 93% complete remission in pediatric patients with r/r ALL [Novartis] "This clinical trial of CTL019 is the largest study of a CART therapy in pediatric patients with relapsed or refractory acute lymphoblastic leukemia, and it is helping us better understand the therapy's potential to achieve durable responses in this patient population."
	5.8.5 ASH - Myélome multiple
Responses Observed in Three-Quarters of Heavily Pre-Treated Multiple Myeloma Patients Receiving KEYTRUDA® (pembrolizumab) Combined With Lenalidomide and Dexamethasone [Merck] In the study with 50 heavily pre-treated patients, initial findings from 17 patients who were treated with KEYTRUDA (pembrolizumab) in combination with lenalidomide and low-dose dexamethasone demonstrated an ORR of 76 percent (n=13/17) (per IMWG 2006), including four very good partial responses (24%) and nine partial responses (53%).
Checkpoint Inhibitors in Multiple Myeloma: Knocking at the Door of a Crowded Market [The OBR Blog] This is the first Phase III trial seeking to add a novel targeted agent onto a Pomalyst/dexamethasone backbone regimen, so this strategy is diving into unknown waters but comes with the advantage of distinguishing Keytruda from the other targeted agents seeking development in combination with doublet regimens.
Study of Bortezomib Added to Revlimid® and Dexamethasone Backbone Therapy Presented at ASH [Celgene] Triplet regimen resulted in significantly improved progression-free survival compared to standard of treatment.
IMiD® Combination Therapies Form Backbone of Multiple Myeloma Research at ASH [Celgene] Nearly 30 combination studies that include IMiD® compounds presented.
ASH 2015: Novel combination approaches for multiple myeloma [ecancer.tv] The panel discuss novel combination approaches to treat multiple myeloma, the role of monoclonal antibodies both as single agent or in combination, and side effect management. They cover several data sets including daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myloma.
Merck immunotherapy Keytruda shows promise in multiple myeloma trial [Reuters] Roger Dansey, head of oncology research for Merck, called the early response sufficient for the company to move the treatment combination into large Phase III trials that could be used to seek approval in multiple myeloma.
	6. Lutte contre les cancers
ASCO and ACS Issue New Guideline on Breast Cancer Survivorship Care [ASCO] The guideline recommendations were developed by a multidisciplinary expert workgroup, with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology and nursing. In addition, a cancer survivor was included to provide a patient perspective. The workgroup conducted a systematic review of literature published through April 2015 and identified 237 relevant articles.
Organizations issue joint guidelines for breast cancer survivors [Reuters] The guidelines issued today by the American Cancer Society and the American Society of Clinical Oncology (ASCO) provide an updated road map to help women and their primary care doctors navigate not just surveillance for new tumors but also a range of mental and physical health problems that can accompany survivorship.
	6.6 Publications
Research Funders and ORCID: New members, mandates, and platforms [ORCID] Researchers rejoice! Funders have been working to integrate ORCID iDs in grant application and reporting workflows, and you should start to experience benefits in the form of single sign on, streamlined application data entry, and reduced post-award reporting burden.
The Importance of Opt-In [ORCID] The Create on Demand process enables the member organization to explicitly request permissions from a researcher (“opt in”) to read and write to that individual’s ORCID record. This process also improves the user experience for researchers with better information flow and fewer clicks to register.
	6.7 DMP, Big Data & applis
Brigham and Women's blames budget woes on electronic records [STAT] The budget overruns and complications are a setback for executives at the Brigham and other hospitals who have argued that implementing new software systems will help contain costs and improve medical care.