Onco Actu du 16 mai 2019

	1. BIOLOGIE
Enzyme PHLPP2 could be a viable drug target for treating prostate cancer [Cold Spring Harbor Lab] In a new study published in the Journal of Cell Biology, researchers were able to halt the natural process of prostate cancer metastasis in mice by deleting the PHLPP2 enzyme.
Single-Cell Methylation Analysis Reveals CLL Evolution, Lineages With Distinct Treatment Responses [Genome Web] A team led by investigators at the New York Genome Center, Weill Cornell Medicine, and the Broad Institute that tracked DNA methylation in individual chronic lymphocytic leukemia (CLL) cells has uncovered relatively consistent epimutation rates in CLL compared with healthy B cells.
Yale study identifies how cancer drug inhibits DNA repair in cancer cells [Yale Cancer Center] The study, published today in the journal Science Translational Medicine, suggests that combining this drug, cediranib, with other agents could potentially deliver a lethal blow in cancer that uses a specific pathway — or process — to create DNA repair cells.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Judge orders FDA to speed up review of e-cigarettes [AP] The American Academy of Pediatrics, Campaign for Tobacco-Free Kids and other groups filed the federal lawsuit in Maryland last year. The groups say the lack of FDA oversight has led to an explosion in underage vaping by teenagers, threatening to hook a generation of Americans on nicotine.
	4.12 BIOPSIES LIQUIDES
Liquid biopsy could identify cancer patients at risk of metastatic disease [ecancer News] Results from the study have been presented at the EACR-ESMO joint conference on liquid biopsies. Researchers analysed liquid biopsies from 47 patients at The Royal Marsden who had localised rectal cancer - i.e. cancer that had not already spread to other body parts.
	4.15 DÉP., DIAG. & PRONO. - IMAGERIE
How to Improve Access to Expertise in Cancer Imaging [ESMO] Practical steps to improve situation in the context of changing landscape of cancer imaging.
	5. TRAITEMENTS
Pancreatic cancer : Promising drug candidate identified [Institut Paoli-Calmettes] These results have just been published in the Journal of Clinical Investigations, and the anti-tumor activity of ZZW-115 is now protected by a patent filed by Inserm Transfert. The exploitation of these results will be entrusted to a new biotechnology company (PanCa Therapeutics), which will be established shortly in the Sud Provence Alpes-Côte d'Azur region, and whose specific objective is to bring this drug into clinical applications.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Cancer could become long-term 'manageable' condition with new class of 'anti-evolution' drugs [The Telegraph] The researchers said the traditional “shock and awe” approach of chemotherapy often fails because it fuels a “survival of the nastiest” competition among any cells not destroyed by the treatment.
Scientists in new push to control cancer before curing it [Reuters] While not abandoning the search for an ultimate cure, the “anti-evolution” project will re-focus on turning cancer into a disease controllable with drugs for many years. This would be a little like HIV, the virus that causes AIDS, the scientists told reporters at a briefing.
World’s first ‘Darwinian’ cancer drug programme aims to deliver step change in cancer treatment [Institute of Cancer Research] The Institute of Cancer Research, London, is to invest an initial £75 million in creating a global centre of expertise in anti-evolution therapies – which hold the promise of outsmarting cancer to improve cure rates.
Cancer: Breakthrough treatments to target drug resistance [BBC News] Chief executive Prof Paul Workman said the institute was "changing the entire way we think about cancer" to focus on anticipating the way cancer cells will evolve to prevent them from becoming resistant to drugs.
New war on cancer aims at longterm survival, not cure [The Guardian] “We believe this will be the first treatment in the world that, rather than dealing with the consequences of cancer’s evolution and resistance, aims to directly confront the disease’s ability to adapt and evolve in the first place.”
	5.10 TRAITEMENTS - ESSAIS
Tagraxofusp Proves Effective for BPDCN, A Rare Blood Cancer [NCI] “The advantage of this drug is that, when it produces a response, it appears to be long-lasting. That’s encouraging,” said Arthur Frankel, M.D., an oncologist at Mitchel Cancer Institute in Mobile, Alabama.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Pfizer, Merck KGaA's latest Bavencio nod sets up 3-way kidney cancer battle [Fierce Pharma] The approval will set Pfizer up for a tough rivalry, not only with Bristol-Myers Squibb, which won FDA approval for a combination of its immuno-oncology drugs Opdivo and Yervoy in first-line kidney cancer last April, but also with Merck—the American one.
FDA approves avelumab plus axitinib for renal cell carcinoma [FDA] Approval was based on JAVELIN Renal 101 (NCT02684006), a randomized, multicenter, open-label trial of avelumab plus axitinib in 886 patients with untreated advanced RCC regardless of tumor PD-L1 expression.
	5.2.3 PHARMA - ÉCONOMIE
FDA tells ImmunoGen to run a second phase 3, sinking stock [Fierce Biotech] ImmunoGen hoped to persuade the FDA to accept a submission based on the subgroup analysis, setting it up to file for approval by the end of 2019. But the FDA saw the primary endpoint fail as a barrier to filing.
ImmunoGen shares tank (again) after the FDA nixes a shot at an OK for its armed antibody in wake of a failed PhIII [EndPoints] Two months after acknowledging that their antibody-drug conjugate mirvetuximab soravtansine failed a Phase III study for ovarian cancer, the FDA has batted back an attempt to hunt an accelerated approval based on a secondary endpoint, sending their stock price tumbling again. The FDA now wants to see a new Phase III trial for the drug, which won’t be cheap or easy to pull off.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Almost half of all new drug approvals in 2018 relied on one clinical trial [EndPoints] "Reliance on a single trial—particularly if that trial is single-arm, unblinded, or evaluates unvalidated surrogate measures as the endpoint—increases the risk to patients that the drug may not work as well as expected (or, separately, may have safety issues that outweigh its benefits). "
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
AbbVie Announces US FDA Approval of VENCLEXTA® (venetoclax) as a Chemotherapy-Free Combination Regimen for Previously Untreated Chronic Lymphocytic Leukemia Patients [AbbVie] Approval based on data from the Phase 3 CLL14 trial of VENCLEXTA® (venetoclax) in combination with obinutuzumab® - a randomized clinical trial to examine stopping an oral-based, chemotherapy-free combination in previously untreated patients with chronic lymphocytic leukemia.
Roche announces FDA approval for Venclexta plus Gazyva for people with previously untreated chronic lymphocytic leukaemia [Roche] Fixed 12-month treatment with Venclexta plus Gazyva significantly reduced risk of disease progression or death by 67% compared to a current standard-of-care.
FDA approves venetoclax for CLL and SLL [FDA] Approval was based on CLL14 (NCT02242942), a randomized (1:1), multicenter, open label, actively controlled trial of venetoclax in combination with obinutuzumab (VEN+G) versus obinutuzumab in combination with chlorambucil (GClb) in 432 patients with previously untreated CLL with coexisting medical conditions.
	5.5.1.1 ASCO (GÉNÉRAL) - INDUSTRIELS
Pfizer Oncology to Showcase New Data from Innovative Science That Address Patient Needs at ASCO 2019 Annual Meeting [Pfizer] Data spans 10 therapies across 10 types of cancer.
New Research from Merck’s Broad Oncology Clinical Development Program to be Presented at 2019 ASCO Annual Meeting [Merck] “At ASCO this year, we look forward to presenting additional overall survival data for KEYTRUDA across different tumor types, as well as first-time LYNPARZA data in pancreatic cancer that reinforce our commitment to helping patients with the most aggressive forms of cancer.”
Seattle Genetics Announces Presentations of New Clinical Data from Multiple Studies of Novel Targeted Therapies at the American Society of Clinical Oncology (ASCO) Annual Meeting [Seattle Genetics] First Presentation of Data from EV-201 Pivotal Trial of Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Cancer Featured in an Oral Session.
Celgene to Highlight New and Updated Hematology and Oncology Clinical Data at Upcoming American Society of Clinical Oncology (ASCO) 2019 Annual Meeting [Celgene] Presentations include innovative cancer research, including novel CAR T technology, as well as key disease areas, including myelofibrosis and multiple myeloma.
Data Presentations at ASCO 2019 Highlight Lilly's Targeted Approach to Developing Treatments for Patients Living with Cancer [Lilly] Lung cancer highlights to include the first presentation of RELAY results and additional findings from KEYNOTE-189. Lilly to share data from Phase 3 ANNOUNCE trial in people with advanced soft tissue sarcoma.
Amgen Showcases Oncology Pipeline At ASCO 2019 [Amgen] First-in-Human Data Evaluating Investigational AMG 510, the First KRASG12C Inhibitor to Reach Clinical Stage, in Solid Tumors.
Janssen to Present Data from Robust Oncology Portfolio and Pipeline at the 2019 ASCO Annual Meeting, Including Best of ASCO Selections [Janssen] Notably, data presentations for ERLEADA® (apalutamide), DARZALEX® (daratumumab) and IMBRUVICA® (ibrutinib) have been selected for the Best of ASCO 2019 Meetings, which highlight cutting-edge science and reflect leading research in oncology.
AstraZeneca continues to redefine cancer treatment at the 2019 ASCO Annual Meeting [AstraZeneca] Presentations highlight Lynparza’s benefit in PARP-mediated cancers and Imfinzi’s three-year overall survival in unresectable, Stage III non-small cell lung cancer.
Shaped like a tennis ball, this cancer protein was thought ‘undruggable.’ Amgen found a way to target it [STAT] Amgen is reporting early but potential progress in an effort to block mutant KRAS and kill cancer cells. The Amgen drug, a small molecule pill called AMG 510, caused tumors to partially shrink in 30% of patients with lung tumors that tested positive for a particular kind of KRAS mutation.
	5.5.10 ASCO (HÉMATO)
Lenalidomide Reduces Risk That Precancer Myeloma Will Progress to Overt Multiple Myeloma in High Risk Individuals [ASCO] At three years, in 87% (phase II) and 91% (phase III) of people with SMM receiving lenalidomide, the condition did not progress to multiple myeloma compared with 66% of people who did not receive the therapy and were just observed for potential progression (phase III).
	5.5.11 ASCO (SNC]
New data for larotrectinib show overall response rates of 94% in children and 76% in adults with TRK fusion cancer; clinical benefit demonstrated in patients with primary central nervous system tumors and brain metastases [Bayer] Larotrectinib is CNS active, and has been exclusively designed to treat TRK fusion cancer in adults and children with an NTRK gene fusion.
Roche’s personalised medicine entrectinib shrank tumours harbouring NTRK, ROS1 or ALK gene fusions in children and adolescents [Roche] Phase I/II study of entrectinib, an investigational medicine, showed responses in all paediatric tumour types harbouring neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) fusions, including those in the central nervous system.
Entrectinib Produces Responses in Children and Adolescents With CNS and Other Cancers That Have Specific Gene Fusions [ASCO] In a phase I/IB study of 29 patients, age 4.9 months to 20 years, with rare central nervous system tumors, neuroblastoma, or other solid tumors, responses to entrectinib, a novel targeted treatment, were seen in 12 of the 28 evaluable patients. The 12 pediatric patients who experienced a response to therapy had fusions in NTRK1/2/3, ROS1, or ALK genes (11 patients) or an ALK mutation (1 patient).
	5.5.15 ASCO (BIOPSIES LIQUIDES)
GRAIL Announces Promising New Data with Early Detection Blood Test to be Presented at 2019 American Society of Clinical Oncology Annual Meeting [Grail] “These initial follow-up data are encouraging and add to the evidence from the CCGA study suggesting this blood test may detect the types of cancers more in need of immediate treatment, rather than contributing to the overdiagnosis of indolent cancers.”
	5.5.16 ASCO (MÉDECINE DE PRÉCISION)
Pediatric MATCH Trial Finds More Frequent Targetable Genetic Alterations in Pediatric Cancers Than Predicted [ASCO] An interim analysis of more than 400 patients screened has revealed the match rate appears to be significantly higher, with 24% of participants eligible to receive treatment with at least one drug being tested in the trial.
	5.5.2 ASCO (SEIN)
Less fat, more fruit may cut risk of dying of breast cancer [STAT] The results are notable because they come from a rigorous test involving 49,000 women over two decades rather than other studies that try to draw health conclusions from observations about how people eat.
Lower-fat diet reduces women’s risk of dying from breast cancer, study says [Washington Post] Women who followed a lower-fat diet rich in fruits, vegetables and grains had a lower risk of dying of breast cancer than those on a higher-fat diet, according to the results of major study.
Balanced, Low-Fat Diet Reduces Risk of Death From Breast Cancer in Postmenopausal Women [ASCO] This is the first large, randomized clinical trial to show that diet can reduce the risk of dying from breast cancer. The study will be presented at the upcoming 2019 ASCO Annual Meeting in Chicago.
	5.5.5 ASCO (GASTRO-INTESTINAL)
Low-Dose Chemotherapy Regimen Effective in Older and Frail Patients With Gastroesophageal Cancer [ASCO] “We hope our finding helps patients make a more informed choice, between low-dose chemotherapy and no chemotherapy at all, with the knowledge that that low-dose chemotherapy can prove beneficial and still allow them to maintain some quality of life while slowing the progression of the disease.”
Clearing up chemo options for frail and elderly patients with advanced oesophageal and stomach cancers [Cancer Research UK] The study included 514 people all over the UK, at an average age of 76, who had advanced stomach or oesophageal cancer. Their doctors knew they wanted to offer chemo, but they weren’t sure of the best dose.
	6.10 POLITIQUES
Big tobacco, the new politics, and the threat to public health [BMJ] With several Tory leadership contenders sympathetic to its ideology, the Institute of Economic Affairs is closer to power than it has been for decades. In an exclusive investigation, Jonathan Gornall reveals how the organisation is funded by British American Tobacco and has links with senior conservative ministers. After orchestrating a series of attacks on public health initiatives, the IEA may now hold the key to No 10.
	6.6 PUBLICATIONS
To meet the ‘Plan S’ open-access mandate, journals mull setting papers free at publication [Science] Questions remain on model’s financial sustainability.
Indonesia tops open-access publishing charts [Nature] European funders have been leading a charge under ‘Plan S’ to make more of the scientific literature free to read. Yet the nations that publish the highest proportion of their research papers open access (OA) aren’t in Europe, according to a preliminary analysis shared with Nature.
Springer Nature journals unify their policy to encourage preprint sharing [Nature] Recognizing the benefits, we move from merely supporting the use of preprint servers to promoting it.