Onco Actu du 1er février 2019

	1. BIOLOGIE
New 3D imaging technique reveals how pancreatic cancers start [The Francis Crick Institute] A new technique to study tissue samples in 3D has revealed that pancreatic cancers can start and grow in two distinct ways, solving a decades-old mystery of how tumours form.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
Smear results for 150,000 women left in backlog amid NHS failings [The Telegraph] The report said delays modernising “complex and ageing IT systems” meant a risk that screening programmes could not identify and invite those eligible for screening.
Health screening 'not meeting targets', report finds [BBC News] None of the three main health screening programmes in England - bowel, breast or cervical - met their targets last year, according to a report by the National Audit Office.
Investigation into the management of health screening [National Audit Office] During 2017-18, more than 7.9 million people were screened under the four programmes covered by this report: abdominal aortic aneurysm, bowel cancer, breast cancer and cervical cancer. In 2018, two events (on the breast and cervical screening programmes) raised concerns about the management and understanding of screening programmes.
NHS England cervical screening backlog revealed by watchdog [The Guardian] National Audit Office finds more than 150,000 untested samples in laboratories.
	4.5 DÉP., DIAG. & PRONO. - COLORECTAL
Colon Cancer Screening Controversy. Here's What All The Debate Is About. [Forbes] If you’re at normal risk and wonder about getting screened at age 45, remember that starting at this age is unproven. We don’t really know, yet, whether screening tests will do you more good than harm.
	4.9 DÉP., DIAG. & PRONO. - SEIN
Technologies to Watch in Breast Imaging [Imaging Technology News] Rising prevalence of breast cancer and other chronic breast diseases, as well as more new technological innovations, will keep this technology on the forefront.
Many Women Get Unnecessary Mammograms Before Breast Reduction Surgery [University of Michigan] Among the women in their 30s who had mammograms before breast reduction surgery, 14 percent went on to have an MRI, ultrasonography or a biopsy in which breast tissue or fluid is removed for laboratory testing. Cancer was found in only 0.5 percent of the women, the study showed.
	5. TRAITEMENTS
Promises, promises, and precision medicine [JCI] In 2000, Francis Collins suggested that “Over the longer term, perhaps in another 15 or 20 years, you will see a complete transformation in therapeutic medicine”. The vision described in the article became the aspirational template for the precision medicine movement. We have passed the 2010 deadline and are rapidly approaching 2020, yet the “complete transformation in therapeutic medicine” has not occurred. Using the framework of the predictions made nearly 20 years ago, we argue that the foundational assumptions of precision medicine are unsound.
Precision Medicine Real Soon Now [In the Pipeline] All those clinics advertising “precision cancer treatment”? Same problem, and worse because of that genomic instability mentioned above. It would be great if we could dial in a personalized treatment for each patient based on tumor sequence, but that’s not where we are yet, outside of very rare cases.
Multi-target drugs should be in the pharma pipeline along with precision drugs [STAT] Even as the use of exquisitely tailored medications continues to expand — the FDA recently approved a cancer treatment called Vitrakvi for use not against a specific type of cancer but for cancers that have a specific genetic mutation — I don’t believe that the pharmaceutical industry should put all of its eggs in the precision medicine basket.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Skin cancer can spread in mice by hijacking the immune system [Cancer Research UK] Researchers also found that one of the chemicals released by Myosin II-rich cells, called interleukin 1A, was key for making cancer cells more invasive. By blocking Myosin II activity with different drugs, they reduced the amount of interleukin 1A produced by melanoma cells in mice and human tumour samples.
Bacteria promote lung tumor development, study suggests [MIT] In mice that were genetically programmed to develop lung cancer, those raised in a bacteria-free environment developed much smaller tumors than mice raised under normal conditions, the researchers found. Furthermore, the researchers were able to greatly reduce the number and size of the lung tumors by treating the mice with antibiotics or blocking the immune cells stimulated by the bacteria.
Researchers Discover Method to ‘Turn Off’ Mutated Melanoma [Boston University] The researchers first identified STK19 (an enzyme encoded by the STK19 gene) to be a critical regulator of NRAS function. Then they characterized the mechanism by which this activation takes place through biochemical and cellular experiments. Finally, they designed an STK19 inhibitor that efficiently prevented NRAS activation and development of NRAS mutant melanoma in an experimental model.
The ‘Complete’ Cancer Cure Story Is Both Bogus and Tragic [Wired] An Israeli company claimed it will cure cancer in a year, and the internet erupted. But in this latest viral incident, everyone loses.
	5.12 IMMUNOTHÉRAPIES
Machine Learning Finds Multiple Factors Underlie Cancer Immunotherapy Success [University of Maryland] The resulting algorithm identified 20 features that, when analyzed together, explained 79 percent of the variation in patient immune responses. According to Leiserson, this means that the unusually comprehensive set of features gathered for these patients is sufficient to predict the patient immune response with high accuracy.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
What’s BMS saying about its Celgene buy behind the scenes? This transcript tells all [Fierce Pharma] One key problem, Boerner pointed out, is that CAR-T therapies are an expensive proposition. “They're expensive from a list price, but when you tack on the logistics of managing them, they're even more expensive,” he said.
Novartis touts record year for manufacturing changes, but Kymriah still an overhang [Biopharma Dive] Novartis sees a big market opportunity for Kymriah (tisagenlecleucel), but manufacturing hiccups have stood in the way.
First patient receives CAR T cell therapy on NHS [Cancer Research UK] “This is an incredibly complex treatment to give,” said Swanton. “Yuvan’s cells were processed in both Europe and the US – and needed collaboration across borders to get the T cell infusion back to London so he could be treated.”
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
FDA Expands Lilly's ALIMTA® (pemetrexed) Label with Combination of KEYTRUDA® (pembrolizumab) and Platinum Chemotherapy for the First-Line Treatment of Metastatic Nonsquamous Non-Small Cell Lung Cancer [Lilly] This indication is approved based on data from Merck's Phase 3 KEYNOTE-189 trial, which enrolled patients regardless of PD-L1 expression and had dual primary endpoints of overall survival (OS) and progression-free survival (PFS).
	5.12.8 IMMUNOTHÉRAPIES - ECONOMIE
Novartis changes NICE's mind on Kymriah, giving CAR-T rival Gilead some company [Fierce Pharma] It’s an about-face for the cost-effectiveness gatekeeper, which initially shot down Kymriah over its high price. But as they often do, talks between the two parties led to a discount on Kymriah’s £282,000 sticker, making way for the therapy’s inclusion on the Cancer Drugs Fund.
NICE recommends another revolutionary CAR T-cell therapy for adults with lymphoma [NICE] The list price for tisagenlecleucel is £282,000 and it is given as a single intravenous infusion. The company have agreed to offer the therapy at a confidential discounted price. It is estimated 200 people will be eligible for treatment each year in the UK and NHS England are working closely with several hospitals across the country to deliver this complex treatment.
	5.2 PHARMA
Johnson & Johnson's Erleada trial stops early on good news, setting up case for new prostate cancer nod [Fierce Pharma] All in all, analysts expect Erleada to eventually cross the blockbuster barrier but not to show up its predecessor. Barclays analyst Geoff Meacham has projected $1.3 billion in peak sales, which is less than half of the $2.71 billion Zytiga pulled in over the first nine months of 2018.
AVEO Oncology Announces NDA Timing Update [Aveo Oncology] AVEO Oncology today announced that it has accepted the recommendation of the U.S. Food and Drug Administration (FDA) not to submit a New Drug Application (NDA) for tivozanib (FOTIVDA®) with the preliminary overall survival (OS) results from the Phase 3 TIVO-3 trial.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
European Commission Consults on Orphan Drug Applications [RAPS] When estimating prevalence of an orphan condition, the revised guideline emphasizes that "the specific epidemiological measure for disease frequency should be stated and justified" and for indirect calculations to estimate prevalence, "all assumptions need to be justified by referring to appropriate scientific literature."
Public consultation on key principles for the electronic product information of EU medicines [EMA] The key principles define an EU-wide approach to support harmonised development and implementation of ePI (electronic product information). They define the various concepts, give examples of the expected benefits of ePI for public health and explain how ePI can be seen in the context of the existing legislative framework, as a complement to the paper package leaflet.
	5.4 TRAITEMENTS - ECONOMIE
IVI Unveils New Value Assessment Model for Non-Small Cell Lung Cancer [IVI] Specifically, the model provides information on the relative value of sequential treatments for epidermal growth factor receptor positive (EGFR+), non-squamous non-small cell lung cancer (NSCLC).
	5.5 ASCO
ASCO Names Advance of the Year: Progress in Treating Rare Cancers [ASCO] Progress Report Debuts ASCO’s Research Priorities for the Cancer Community, Emphasizes Impact of Federal Funding.
Clinical Cancer Advances 2019: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology [JCO] ASCO’s 2019 Advance of the Year, Progress in Treating Rare Cancers, reflects the impressive gains we have made in understanding these so-called orphan diseases and in tailoring treatments to target their unique characteristics.
	5.9.1 ASTRO
High-dose radiation therapy improves long-term survival in patients with stage-IV cancers, trial finds [ASTRO] In this phase II trial, Dr. Heron and his colleagues enrolled 147 patients across three large cancer centers to evaluate the safety and feasibility of stereotactic radiation for a variety of oligometastatic cancers — that is, cancers that had been previously treated but then returned in a limited number of other parts of the body.
	6. LUTTE CONTRE LES CANCERS
Cancer patients in poor countries needlessly denied pain relief: WHO [Reuters] Two-thirds of industrialized countries have oral morphine, an opioid widely used to lessen severe pain, available in more than half of their pharmacies, against only 6 percent of poor countries, WHO expert Dr Cherian Varghese said.
	6.10.1 POLITIQUES (USA)
Romney to drug industry CEOs: ‘Change is coming’ [STAT] Romney’s tough talk is the latest sign that Republicans, despite their once friendly relationship with the drug industry, are increasingly pushing for drug pricing reform.
	6.6 PUBLICATIONS
Few open-access journals meet requirements of Plan S, study says [Science] Frantsvåg and Strømme say they aren’t arguing against Plan S. “But we want to warn that the current timeline will pose a threat to a number of open access journals of good scholarly quality that scholars do not want to lose,” they write.
	6.9 CONTROVERSES
A new NIH rule won’t be enough to make clinical research more inclusive [STAT] Under the National Institutes of Health’s new Inclusion Across the Lifespan policy, federally supported medical research must include patients of all relevant ages or explain their exclusion. Since most studies already include adults, and a mandate to include children has existed since 1998, the novelty in this policy is the stipulation that clinical research include people age 65 and older.