Onco Actu du 9 mai 2019

	1.4 BIOLOGIE - TECHNOS
The new techniques revealing the varied shapes of chromatin [Nature] Researchers are realizing that the DNA–protein complex doesn’t just have one form but many.
	3.1 PRÉVENTION - TABAC
Walmart Raises Minimum Age to Buy Tobacco Products to 21 [NY Times] Walmart will also no longer sell “fruit- and dessert-flavored electronic nicotine delivery systems” and other devices for vaping, according to the company’s announcement.
Walmart raises U.S. tobacco purchase age to 21 starting in July [Reuters] The increased pressure on retailers comes at a time when states and cities across the United States have moved to raise the legal age for purchasing tobacco in an effort to prevent addiction at young ages.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Vaping companies facing European opposition to higher nicotine level [Reuters] The roll-out across European Union countries of Juul, whose devices resemble a USB flash drive and work by vaporizing a nicotine-laced liquid, has been hampered by limits of 20 milligrams of nicotine per millimeter of liquid compared to 59 in the United States. This, the company says, makes it less effective as an alternative to cigarettes for heavy smokers.
	3.3 PRÉVENTION - VACCINS
Merck's Gardasil blockbuster sales prompt $1B plant expansion [Fierce Pharma] Merck & Co. has been experiencing a surging wave of Gardasil sales that it expects to ride for some time yet. To maintain the momentum, the drugmaker says it will spend $1 billion to expand production.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
Cancer risk tools underused in general practice, research shows [University of Exeter] In a survey of 476 GPs working in 277 general practices in the UK, the researchers discovered that the tools are only available for use in one-third of practices, although this should increase as the tools are integrated into more IT systems in the future. Crucially, the survey found that the tools are only likely to be used in around a half of those practices that have access.
	4.9 DÉP., DIAG. & PRONO. - SEIN
Using AI to predict breast cancer and personalize care [MIT] The team’s model was significantly better at predicting risk than existing approaches: It accurately placed 31 percent of all cancer patients in its highest-risk category, compared to only 18 percent for traditional models.
Efforts to Improve Mammography Highlight Breast Density [JAMA] For the first time in more than 20 years, the FDA has proposed amendments to key regulations to help improve the quality of mammography services and aid patients and physicians in making more informed medical decisions.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Study shows MD Anderson-developed drug effective in overcoming ibrutinib resistance in mantle cell lymphoma [MD Anderson Cancer Center] Inhibition of OXPHOS with IACS-10759 results in marked growth inhibition in vivo and in vitro in ibrutinib-resistant, patient-derived cancer models.
New study exposes key vulnerability of rare pediatric kidney tumor, reveals potential treatment [Dana-Farber Cancer Institute] Using a trio of complementary, large-scale approaches — including RNA interference (RNAi), CRISPR-Cas9 genome editing, and small molecule screening — the researchers homed in on UPS as a critical vulnerability that unfolds as a result of SMARCB1 loss. Additional experiments confirmed this finding: when RMC cells are exposed to the drug ixazomib, a type of proteasome inhibitor, they die.
New treatment could become first ever targeted therapy designed for ‘untreatable’ childhood brain cancer [Institute of Cancer Research] The new type of drug targets the protein molecule produced by mutated versions of the ACVR1 gene found in the deadly childhood brain cancer ‘diffuse intrinsic pontine glioma’ (DIPG).
	5.10 TRAITEMENTS - ESSAIS
AstraZeneca's Calquence preps for Imbruvica showdown with phase 3 CLL win [Fierce Pharma] The Ascend trial is one of two in CLL the British drugmaker expects to read out this year, alongside Elevate-TN, which is testing Calquence in previously untreated CLL. The med is also in two other phase 3 CLL trials, AZ said.
AstraZeneca blood cancer drug hits study goal early [Biopharma Dive] The news gives a lift to the British pharma's hopes for the drug, which was approved in late 2017 for a type of lymphoma. While AstraZeneca has seen success with its drugs for solid tumors, its blood cancer business rests entirely on Calquence.
Calquence Phase III ASCEND trial met primary endpoint at interim analysis in relapsed or refractory chronic lymphocytic leukaemia and will stop early [AstraZeneca] Calquence (acalabrutinib) significantly increased the time patients live without disease progression.
Watch out AbbVie and J&J, AstraZeneca just took another big swing at one of your star cancer drug franchises [EndPoints] AstraZeneca reported Tuesday that its BTK contender Calquence (acalabrutinib) aced a Phase III trial as a second-line therapy for chronic lymphocytic leukemia patients, allowing researchers to call it early as they position this drug for greener pastures.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Clinical Trial Underway for a Natural Killer Cell Therapy [The Scientist] In a first-of-its-kind clinical trial, a natural killer cell immunotherapy derived from induced pluripotent stem cells is being tested for safety in 64 patients with a variety of solid tumors.
	5.12.4 IMMUNOTHÉRAPIES - ESSAIS
Keytruda PhIII failure in gastric cancer blights Merck’s quest for frontline dominance [EndPoints] Merck went ahead with the Phase III trial despite a flop in the second-line setting of the same indication in 2017.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Regeneron’s star bispecific is linked to 2 deaths in a small study — which was no help for its Q1 call [EndPoints] Regeneron execs chose to disclose in their Q1 call with analysts today that their closely watched bispecific REGN1979 was linked with two deaths from cytokine release syndrome in a small PD-1 combo study involving 30 patients.
	5.12.7 IMMUNOTHÉRAPIES - VACCINS
A Vaccine to Treat Non-Hodgkin Lymphoma Advancing in Clinical Trials [NCI] The Mount Sinai team’s newly launched trial will pair the vaccine with the checkpoint inhibitor pembrolizumab (Keytruda) in people with advanced indolent NHL, breast cancer, and head and neck cancer.
	5.12.8 IMMUNOTHÉRAPIES - ECONOMIE
NICE lung cancer U-turn boosts NHS treatment options in England [Cancer Research UK] After consultation with the company on how the information from a key clinical trial was assessed, NICE agreed a new way of evaluating the treatment. Based on this, NICE decided that the treatment’s cost was under the threshold for how much the NHS would pay.
	5.2 PHARMA
AstraZeneca and Daiichi's HER2 ADC hits goal in pivotal trial [Fierce Biotech] Phase 2 results in line with those numbers would set AstraZeneca and Daiichi up to position the ADC as an option for HER2+ breast cancer patients who progress following treatment with Roche’s drugs.
Daiichi Sankyo Announces [Fam-] Trastuzumab Deruxtecan Demonstrated Clinically Meaningful Response in Patients with Refractory HER2 Positive Metastatic Breast Cancer, a Population with High Unmet Need [Daiichi Sankyo] Daiichi Sankyo and AstraZeneca plan to present the data from DESTINY-Breast01 at an upcoming medical meeting.
AstraZeneca’s $7B bet on Daiichi Sankyo’s antibody drug conjugate pays off with pivotal data to back their regulatory pitches [EndPoints] The drug, trastuzumab deruxtecan, is an antibody drug conjugate (ADC) — therapeutics in which a cancer-killing toxin is attached to a specific antibody using a biodegradable linker — for cancers that express HER2, a protein associated with aggressive disease that often resides on certain breast cancer cells.
AstraZeneca-Daiichi breast cancer treatment shows promise in latest study [Reuters] Daiichi and the British drugmaker said they planned to seek approval for the drug with the U.S. Food and Drug Administration in the second half this year.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
BioNTech snaps up struggling MabVax's lead asset, labs, eyeing San Diego R&D site [Fierce Biotech] according to the company. This med works as a fully human IgG1 monoclonal antibody targeting sialyl Lewis A (sLea), an epitope expressed in pancreatic and other gastrointestinal cancers that plays a role in how tumors stick to organs and how they spread to other parts of the body.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
European Commission Approves LORVIQUA® (lorlatinib) for Certain Adult Patients with Previously-Treated ALK-Positive Advanced Non-Small Cell Lung Cancer [Pfizer] The conditional marketing authorization was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs.
	6. LUTTE CONTRE LES CANCERS
American Cancer Society Sets 2035 Challenge Goals [ACS] Mortality goal based on applying outcomes among healthier segments to entire population.
The American Cancer Society 2035 challenge goal on cancer mortality reduction [CA: A Cancer Journal for Clinicians] The greatest pay‐off in terms of cancer deaths prevented is through continued work on tobacco control, followed by an effort to control excess body weight. This would require a change in the behavior of the US population and culture of a magnitude very similar to that of the changes regarding smoking since the mid‐1960s.
	6.1 OBSERVATION
Rising rural body-mass index is the main driver of the global obesity epidemic in adults [Nature] Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017.
Postmenopausal women who used to smoke 'at lower risk of bladder cancer' than smokers, says study [Cancer Research UK] The research analysed data from the Women’s Health Initiative, a long-running US-wide study of postmenopausal women which included smoking habits data from 143,279 participants.
NIH says its 1-million-person health study is off to good start [Science] The All of Us study run by the National Institutes of Health (NIH) in Bethesda, Maryland, has recruited 143,000 participants who have already taken surveys and visited a clinic to give blood and urine samples. Another 87,000 have at least registered for the study.
	6.10.1 POLITIQUES (USA)
Drug makers will have to include prices in TV ads as soon as this summer [STAT] The announcement is also significant because it represents the first big-picture drug pricing proposal that the Trump administration has finalized.
List prices in drug ads on TV coming as CMS finalizes rule [EndPoints] As far as enforcement of the rule, the CMS does not plan to force companies to comply, other than by maintaining an annual list of drugs that have violated the rule.
Drug Prices Will Soon Appear in Many TV Ads [NY Times] A disclaimer will also state, “if you have insurance that covers drugs, your cost may be different,” according to officials at the Department of Health and Human Services.
U.S. government to require drugmakers to show prices in TV ads [Reuters] The advertising rule, which was finalized on Wednesday, will take effect in about 60 days. It was originally suggested as part of President Donald Trump’s “blueprint” to lower U.S. drug prices last May.
	6.11 PATIENTS
‘The most peaceful sleep’: Cancer is nudging me to picture dying in a new way [STAT] Death as an abstract concept is probably a lot less terrifying than staring it in the face. But I’ll remember what my grandparents said and try to move forward with the same kind of contented pragmatism they shared with me.
	6.12 ETHIQUE
We need more signal and less noise about industry payments to doctors [STAT] In its current form, transparency of industry payments hasn’t helped patients distinguish between the true signal of their own doctors’ industry interactions — or lack of them — from the noise of all other doctors’ behaviors. My colleagues and I believe there are several things that can be done to enhance the signal-to-noise ratio.
Radiation therapy consent forms too difficult to read [Reuters] The study wasn’t designed to assess whether the reading levels of consent forms might directly impact patients’ treatment decisions. It’s also possible that doctors explained the risks and benefits of radiation in language very different than what was used on the forms.
David Shaw: The hidden harms of “genomic volunteering” [BMJ] While genome sequencing certainly aids medical research, at least three major ethical issues are raised by this new scheme.
	6.3 ASSOCIATIONS/FONDATIONS
Act now to end the postcode lottery in early diagnosis of ovarian cancer [Target Ovarian Cancer] Demand change: write to the Prime Minister.
Women are having lives cut short because GPs miss symptoms of ovarian cancer, study suggests [The Telegraph] Research by the charity Target Ovarian Cancer found that in some parts of the country, just 29 per cent of cases are being spotted early, when the disease is less likely to prove fatal.
	6.4 MÉDICO-ÉCO
Global study predicts more than 50 percent rise in chemotherapy demand by 2040 [MedicalXPress] Between 2018 and 2040, the number of patients requiring first-line chemotherapy treatment each year is predicted to rise from 9.8 million to 15 million (53%) globally, if there were full application of evidence-based guidelines. This is according to a modelling study published in The Lancet Oncology journal.
	6.6 PUBLICATIONS
Reproducibility and Replicability in Science [National Academies Press] While reproducibility is straightforward and should generally be expected, the report says, replicability is more nuanced, and in some cases a lack of replicability can aid the process of scientific discovery. This report provides recommendations to researchers, academic institutions, journals, and funders on steps they can take to improve reproducibility and replicability in science.
If At First You Don’t Succeed … Make Another Response to Plan S? [Scholarly Kitchen] While the cOAlition rebuffed Springer Nature’s recommendations in their first response to the draft guidance, perhaps this second attempt will find a receptive audience? I imagine not, given the “no hybrid” principle of Plan S.