Onco Actu du 3 janvier 2019

	1. BIOLOGIE
Mutations differ in normal and cancer cells of the oesophagus [Nature] What determines whether genetic mutations lead to cancer? Analyses of healthy cells in the human oesophagus reveal that a high level of genetic alterations arises as people age, yet this doesn’t usually result in cancer.
Cancer Driver Gene Mutations Rise with Age in Otherwise Normal Esophageal Tissue [Genome Web] Although such driver gene mutations typically turned up in physiologically unaltered tissue before late adolescence, the researchers noted, their results suggest clones containing these mutations expand significantly not only with age but also in individuals who reported heavy smoking and drinking — known lifestyle contributors to esophageal cancer risk.
‘For 30 years I’ve been obsessed by why children get leukaemia. Now we have an answer’ [The Guardian] In other words, a susceptible child suffers chronic inflammation that is linked to modern super-clean homes and this inflammation changes his or her susceptibility to leukaemia so that it is transformed into the full-blown condition.
	2. ETIOLOGIE
Bacon-cancer link: head of UN agency at heart of furore defends its work [The Guardian] The head of the UN agency that provoked a massive outcry and some ridicule when it declared that bacon, red meat and glyphosate weedkiller caused cancer has defended its work, denying the announcements were mishandled and insisting on its independence.
	2.7 ETIOLOGIE - OBÉSITÉ
Proportion of Cancers Associated with Excess Body Weight Varies Considerably by State [ACS] Cancers related to body weight twice as predominant in women than in men.
Obesity explains almost 1 in 20 cancer cases globally [Reuters] Overweight and obesity has been definitively linked to an increased risk of 13 cancers affecting the breast, colon and rectum, uterus, esophagus, gallbladder, kidney, liver, ovary, pancreas, stomach, and thyroid, brain and spinal cord, and blood cells.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Public Health England maintains vaping is 95% less harmful than smoking [The Guardian] As scepticism rises, PHE says e-cigarettes could help more people quit smoking.
Juul Closes Deal with Tobacco Giant Altria [NY Times] Altria agreed to pay $12.8 billion to acquire a 35% stake of the popular vaping start-up. Public health advocates criticized the union.
FDA chief to meet e-cigarette makers amid crackdown [Reuters] In a rare move last week, the U.S. Surgeon General Jerome Adams issued an advisory urging aggressive steps against e-cigarette use among teens, which he said has become an “epidemic”.
	3.3 PRÉVENTION - VACCINS
The HPV Vaccine: Increasing the Use of an Important Cancer Prevention Tool [NCI] Dr. Barbara Rimer, chair of the President’s Cancer Panel, summarizes the panel’s recent report on the HPV vaccine, which includes priorities and strategies to ensure that more people receive this critical cancer vaccine.
	3.8 PRÉVENTION - ALIMENTATION
Stop adding cancer-causing chemicals to our bacon, experts tell meat industry [The Guardian] “Government action to remove nitrites from processed meats should not be far away,” Malhotra said. “Nor can a day of reckoning for those who dispute the incontrovertible facts. The meat industry must act fast, act now – or be condemned to a similar reputational blow to that dealt to tobacco.”
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
A breath test with the goal of detecting multiple cancers is ready to start trials [Cancer Research UK] Fitzgerald says the most important thing about this trial is the design. “We’re not just doing this retrospectively with people with advanced cancer,” she says. Instead, the trial will recruit people who have gone to their doctor because they have potential symptoms of cancer, or because they have a condition that puts them at a higher risk of developing the disease.
Clinical trial launches to develop breath test for multiple cancers [Cancer Research UK] When cells carry out biochemical reactions as part of their metabolism they produce a range of VOCs. If their metabolism becomes altered, such as in cancer and various other conditions, cells can release a different pattern of VOCs. The researchers aim to identify these patterns using Owlstone Medical’s Breath Biopsy® technology.
Could cancer be detected in the breath? Cancer Research UK launches major trial to find out [The Telegraph] In tests run by Cancer Research UK, breath samples from 1,500 people will be collected in the hope that odorous molecules called volatile organic compounds (VOCs) can be detected. All cells produce VOCs through their normal day-to-day operation, but if their metabolism changes, such as in cancer, they release a different pattern.
UK scientists test breathalyser for detecting early cancers [The Guardian] The two-year trial, taking place at Addenbrooke’s hospital in Cambridge, is recruiting 1,500 participants, including healthy individuals as well as cancer patients. Initially, patients with suspected oesophageal and stomach cancers will be asked to try the test. Later it will be extended to include prostate, kidney, bladder, liver and pancreatic cancers.
	4.10 DÉP., DIAG. & PRONO. - FDA, EMA, NICE,...
FDA Formally Recognizes First Public Genetic Information Database [FDA Law Blog] By formally recognizing public genetic information databases, FDA permits sponsors to use information from a recognized database as a source of valid scientific evidence to support the clinical validity of genetic and genomic-based in vitro diagnostic.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Personalized Medicine 2018: More Drugs, Greater NGS Adoption, Growing Appreciation of Dx Value [Genome Web] "All of us in the personalized medicine community have a responsibility to understand how we can help patients ask for the right tests," said Keeling. "It's complex … but that does not mean we should ignore the inevitable fact that ultimately the patient will drive precision medicine."
The Limits of Personalized Medicine: You Don't Need 800 Cable Channels (Or Tumor Genetic Mutations) [Medscape] Having waded through NGS reports myself for the past several years, I would argue that there is good reason to believe that they create a murky mess rather than a clear picture.
	4.9 DÉP., DIAG. & PRONO. - SEIN
Three breast cancer relapse tests recommended for NHS use [Cancer Research UK] Earlier this year, a clinical trial showed that the Oncotype Dx test could be used to tailor treatment for women with early stage breast cancer. Those with an intermediate risk of their cancer coming back after surgery, as judged by the test, could be spared chemotherapy after surgery, according to the trial. NICE has now also added two other relapse tests to its recommendation: EndoPredict and Prosigna.
	5.12 IMMUNOTHÉRAPIES
Yale Cancer Center Scientists Advise Caution in Immunotherapy Research [Yale] Lieping Chen, MD, PhD, who pioneered work on the PD-1/PD-L1 pathway, cautions that some immunotherapy research is going off track by moving into drug development without a firm foundation of basic biological understanding.
	5.12.10 IMMUNOTHÉRAPIES - FUSIONS ET ACQUISITIONS
Novartis announces offer to acquire CellforCure to expand manufacturing capacity for innovative cell and gene therapies [Novartis] Under the proposed agreement, Novartis would acquire the share capital of CellforCure from LFB including the cell and gene manufacturing facility located in Les Ulis and the related adjacent land.
Can Novartis slim down CAR-T manufacturing timelines with its latest acquisition attempt? [EndPoints] The CDMO is based in Les Ulis near Paris, operating what it describes as one of the first and largest platforms in Europe for cell and gene therapy.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Merck KGaA hands off its CAR-T R&D operations to Intrexon in $175M deal [EndPoints] The German Merck is characterizing the move as an R&D simplification process, staying focused where they believe they can make the most progress. And the deal comes three years after the two companies allied on CAR-T, with Intrexon contributing its tech — including Sleeping Beauty — for the preclinical work underway.
Next-gen T cell player TCR2 Therapeutics sets stage for $100M-plus IPO as MPM’s Baeuerle caps prolific year [EndPoints] In contrast to existing T cell therapies, the TCR2 technology is fashioned such that it could be used across patients that express the cancer surface antigen irrespective of human leukocyte antigens (HLA) subtype, which could potentially address a larger group of patients.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
Pfizer, Merck KGaA's Bavencio takes a hit with second ovarian cancer failure [FiercePharma] For now, Pfizer and Merck KGaA aren’t giving up on Bavencio’s ovarian cancer prospects altogether. They’re still testing the drug in combination with Pfizer’s Talzenna, a member of the PARP inhibitor class that’s made waves in ovarian cancer treatment over the last few years.
Pfizer, Merck KGaA hit the brakes on another PhIII as PD-L1 Bavencio flops yet again [EndPoints] Pfizer and Merck KGaA are cementing in their distant runner-up status for Bavencio (avelumab), a PD-L1 checkpoint that just failed its fourth late-stage trial. And the drumbeat of setbacks — at a time checkpoints are proliferating around the world — will hurt their prospects for making this the blockbuster they both need.
Merck KGaA-Pfizer to end late-stage ovarian cancer treatment study [Reuters] The results showed the drug, Bavencio, in combination with, or as a follow-on treatment to, platinum-based chemotherapy could not achieve the primary goal of progression-fee survival in patients.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
Merck Provides Update on KEYTRUDA® (pembrolizumab) Supplemental Biologics License Application (sBLA) for KEYNOTE-042 Trial [Merck] The sBLA is based on results of the Phase 3 KEYNOTE-042 trial where KEYTRUDA monotherapy demonstrated a significant improvement in overall survival compared with chemotherapy in this patient population.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Early access to Tecentriq combination granted through EAMS [Pharma Times] The decision was made following a positive scientific opinion by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), and was based on results from a subgroup of patients in the Phase III IMpower150 study.
China greenlights second homegrown PD-1 in 10 days as Innovent celebrates its first drug OK with Eli Lilly [EndPoints] Sintilimab is the fourth checkpoint to be approved in China and, so far, the only one jointly developed by a multinational drugmaker and a local biotech (the other two are Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo).
	5.12.8 IMMUNOTHÉRAPIES - ECONOMIE
As immuno-oncology heads into 2019, one thing is clear: It’s good to be Merck [FiercePharma] Of course, Keytruda’s success hasn’t been confined to lung cancer—and it won’t be in 2019, either. The drug already has investors at Bristol-Myers Squibb quaking in their boots over the prospect of a speedy kidney cancer approval that could diminish Opdivo’s market share. And as the drug advances in other tumor types, shareholders could punish Merck’s rivals, too.
Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people aged up to 25 years [NICE] The most plausible cost‑effectiveness estimates for tisagenlecleucel are higher than what NICE normally considers acceptable. The life expectancy of people with relapsed or refractory acute lymphoblastic leukaemia is uncertain. It does not meet both of NICE's criteria to be a life-extending treatment at the end of life. Therefore tisagenlecleucel cannot be recommended for routine use in the NHS.
	5.2 PHARMA
Astellas and Pfizer Announce Positive Top-Line Results from Phase 3 ARCHES Trial of XTANDI® (enzalutamide) in Men with Metastatic Hormone-Sensitive Prostate Cancer [Pfizer] Detailed results will be submitted for presentation at an upcoming medical congress.
Novartis announces new CEO of Oncology Business Unit [Novartis] Susanne Schaffert joined Novartis more than 20 years ago and has spent the last six years in the Oncology business in leadership roles, including Region Head, Novartis Oncology Europe, where she led that organization through 5 years of sustained growth (excluding Glivec® which lost exclusivity during this period).
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
Novartis successfully completes acquisition of Endocyte [Novartis] Adds 177Lu-PSMA-617, a potential first-in-class radioligand therapy in Phase III development for metastatic castration-resistant prostate cancer (mCRPC).
	5.3 TRAITEMENTS - FDA, EMA, NICE...
At the end of a bumper year for approvals, FDA hit by government shutdown [FierceBiotech] “Many asked if #FDA can accept new medical product applications during the shutdown. The #FDA can't collect FY 2019 user fee payments during the shutdown, which means we can't accept new applications for products under user fee programs: PDUFA, GDUFA, BsUFA, MDUFA, ADUFA, AGDUFA.”
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
Novartis receives European Commission (EC) approval for expanded indication for Kisqali® (ribociclib) [Novartis] Kisqali is now approved in the European Union (EU) for the treatment of women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) locally advanced or metastatic breast cancer in combination with fulvestrant as initial endocrine-based therapy and in women who have received prior endocrine therapy.
	5.4 TRAITEMENTS - ECONOMIE
Targeted drug not approved for certain lymphoma patients on the NHS [Cancer Research UK] The National Institute for Health and Care Excellence (NICE) concluded that giving brentuximab vedotin (Adcetris) to people with a type of lymphoma after they’ve had another treatment is not cost effective. The decision will be reviewed in February.
	6. LUTTE CONTRE LES CANCERS
Signs of progress and challenges as more patients survive cancer [Reuters] Part of the problem is that there aren’t clear quality benchmarks for measuring or improving survivorship care. Most quality measures focus on treating tumors, not on helping survivors navigate life afterward, the new report notes.
	6.1 OBSERVATION
Missed cancer screenings linked to earlier death from non-cancer causes [Reuters] “What probably accounts for this association is the fact that people who follow advice to undergo screening have a lot of other health-related behaviors,” Grady added. “It’s likely that it’s these sorts of behaviors that reduce the risk of dying.”
Study finds elevated risk of certain rare blood cancers after chemotherapy for most solid tumors [NCI] They analyzed SEER registry data on more than 700,000 patients age 20–84 in the United States with solid tumors who were diagnosed and treated with initial chemotherapy during 2000–2013 and survived at least one year after diagnosis. Of these patients, 1,619 developed tMDS/AML through 2014.
	6.11 PATIENTS
In Praise of Gentleness [NY Times] I’ve been lucky that most of my care is delivered with tenderness, despite the fact that cancer patients are routinely exposed to brutal procedures.
	6.12 ETHIQUE
Memorial Sloan Kettering’s Season of Turmoil [NY Times] “I don’t think you can serve two masters,” said Dr. Bernard Lo, who led an influential Institute of Medicine panel in 2009 that investigated financial conflicts in medicine. “The whole reason for being in the cancer care business is that you’re trying to help people in need, and that’s not at all the company’s main purpose. It’s to generate profits on their products.”
When Doctors Serve on Company Boards [NY Times] Cancer centers are re-evaluating their relationships with health care companies, including when, if ever, doctors and researchers should serve on corporate boards. Here are some hospital executives and cancer researchers who sit on the boards of publicly traded companies, in dual roles that may raise questions about conflicts of interest.
	6.4 MÉDICO-ÉCO
A double diagnosis — cancer while poor [Boston Globe] Medical science has a name for the damaging economic side effects of serious illness — “financial toxicity.”
	6.5 MÉDECINES ALTERNATIVES/COMPLÉMENTAIRES
China regulator probes TCM firm after cancer case sparks online furor [Reuters] Authorities in China are investigating a traditional Chinese medicine (TCM) firm linked to the death of a young girl with cancer, after the case was rekindled online and reignited widespread anger over perceived failings in healthcare.
	6.6 PUBLICATIONS
Journals are failing to address duplication in the literature, says a new study [Retraction Watch] Our main finding is that duplicate publications are not addressed – in our study only 54 % (n=194 of 359) of duplicates were addressed by journals and only 9% (n=33) retracted, although they should all have been retracted according to editorial standards (e.g. COPE).
	6.7 DMP, BIG DATA & APPLIS
Anonymous patient data may not be as private as previously thought [Reuters] “More broadly the study suggests that other types of health data that have been thought to be non-identifying could potentially be matched to individuals by using machine learning and other artificial intelligence technologies.”
	6.7.3 DMP
Full patient records to be available online under NHS IT shake-up [The Guardian] All NHS patients in England will be able to book GP appointments online, order repeat prescriptions and access their full medical history on a new cloud system as part of a shake-up of IT systems.
	6.9 CONTROVERSES
After damaging Reuters report, J&J doubles down on talc safety message [Reuters] The Dec. 19 tweet claiming that the FDA’s own tests never found asbestos in J&J talc, for example, ignores an agency scientist’s 1973 finding that a Shower to Shower sample contained asbestos fibers, according to a copy of an FDA report titled “Asbestos and Other Contaminants in Talc” and a deposition of a former J&J head toxicologist. The FDA did not respond to questions for this article, citing a partial government shutdown.