Onco Actu du 12 février 2019

	1. BIOLOGIE
A new pattern of DNA tags points to a ‘seed’ for cancer [Garvan Institute] In normal cells, Dr Skvortsova discovered, CpG island borders are covered in so-called hydroxymethyl tags that are known to remove methyl tags – a ‘cleaning’ process, which the team’s findings suggest is disrupted in cancer.
Tackling tumour scar tissue could be key to treating pancreatic cancer [Institute of Cancer Research] By looking at pancreatic cancer samples from 16 patients in the UK, Germany and Australia, and 50 surgically resected tumours from France, the study, published in the Journal of Pathology, now shows that there are at least four different types of scar tissue, and each may influence the cancer in a different manner.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Statement from FDA Commissioner Scott Gottlieb, M.D., on new data demonstrating rising youth use of tobacco products and the agency’s ongoing actions to confront the epidemic of youth e-cigarette use [FDA] Based on a growing body of evidence, I fear the youth trends will continue in 2019, forcing us to make some tough decisions about the regulatory status of e-cigarettes. The signs that we’re seeing are not encouraging.
Tobacco use is soaring among U.S. kids, driven by e-cigarettes [Axios] Public health officials on Monday said there's a growing epidemic of tobacco products currently used by children — 4.9 million high school and middle school kids used tobacco products in 2018 up from 3.6 million in 2017 — mainly due to a growth in e-cigarette usage.
Number of US teens using e-cigarettes surges to 5m in one year – study [The Guardian] Vaping among young people increased by 1.5 million in 2018, prompting calls for regulation.
	4.9 DÉP., DIAG. & PRONO. - SEIN
Study: Mammograms helped prevent half a million deaths in last 30 years [UPI] In 2018, mammography examinations and breast cancer treatment reduced the expected mortality rate to 58.3 percent -- a 45 percent decline -- according to a study published Monday in the journal Cancer.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
New therapeutic target found for aggressive pediatric cancers with few treatment options [MD Anderson Cancer Center] Preclinical study identifies vulnerability in orphan cancers with SMARCB1 mutations, spurs launch of Phase II clinical trial.
Interaction between immune factors triggers cancer-promoting chronic inflammation [Mass. General Hospital] Mass. General study finds that blocking IL-33/Treg axis prevents development of skin and colon cancer in mice with chronic inflammation.
	5.12 IMMUNOTHÉRAPIES
Glioblastoma Markers of Checkpoint Immunotherapy Response Discovered [Genome Web] As they reported today in Nature Medicine, the researchers retrospectively analyzed longitudinal samples from 66 individuals with GBM who were treated with anti-PD-1 drugs such as nivolumab or pembrolizumab at disease recurrence after prior chemo- and radiotherapies, including 17 GBM patients with long-term immunotherapy responses.
	5.12.1 IMMUNOTHÉRAPIES - PARTENARIATS
AbbVie Joins Myeloma Race with $90M Deal for Rights to Teneobio Drug [Xconomy] With the Teneobio deal, AbbVie joins a number of companies aiming to treat multiple myeloma by going after cancer cells that produce a protein called B-cell mutation antigen, which is found at higher levels in multiple myeloma cells.
AbbVie, Teneobio ink $90M deal to develop BCMA bispecific for multiple myeloma [Fierce Biotech] By targeting BCMA and CD3, the asset, dubbed TNB-383B, is designed to direct the body's own immune system to target and kill BCMA-expressing tumor cells. It is one of four preclinical programs in Teneobio’s pipeline. The other three are a trispecific antibody for the treatment of lymphoma, a bispecific for HIV and checkpoint inhibitors that are mono- and bispecific.
AbbVie and Teneobio Announce a Strategic Transaction to Develop a New Treatment for Multiple Myeloma [AbbVie] TNB-383B is a bispecific antibody that simultaneously targets BCMA and CD3, utilizing Teneobio's unique anti-CD3 platform. Through this dual targeting mechanism, TNB-383B is designed to direct the body's own immune system to target and kill BCMA expressing tumor cells.
	5.12.4 IMMUNOTHÉRAPIES - ESSAIS
An early study ‘infuses hope’ back into attempts to use immunotherapy to treat brain cancer [STAT] Researchers aren’t sure why the patients who received pembrolizumab before surgery lived longer, but it’s possible that providing the drug and surgery in that order amounted to a one-two punch.
For recurrent glioblastoma, immunotherapy before surgery appears to help more than afterward [UCLA] The trial, which took place at seven medical centers throughout the U.S., evaluated 35 people with recurrent and surgically resectable glioblastoma — meaning the tumors could be removed by surgery. Of them, 16 received pembrolizumab before their surgeries and 19 received the drug afterward. Those who received the drug before surgery survived an average of 417 days, those who received the drug after surgery lived an average of 228 days.
Immunotherapy may help patients with the kind of cancer that killed John McCain [Washington Post] Glioblastoma is one of the deadliest of cancers, killing almost all its victims, who have included Ted Kennedy, John McCain and Beau Biden. But a new, early phase study offers a sliver of hope that drugs that rally the immune system may help some patients live longer.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Merck's Keytruda looks to zoom past Opdivo with fast head and neck cancer review [Fierce Pharma] FDA staffers based their decision on data Merck trotted out at last year’s European Society for Medical Oncology (ESMO) meeting in October.
FDA promises speedy review on moving Merck’s Keytruda up as first-line head and neck cancer therapy [EndPoints] An approval here — for the frontline use of Keytruda in head and neck cell carcinoma, both as a monotherapy and in combination with chemo — would follow an accelerated approval for recurrent or metastatic cases granted in 2016.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
European Commission Approves Bristol-Myers Squibb’s Sprycel (dasatinib) in Combination with Chemotherapy for Treatment of Pediatric Patients with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia [BMS] The approval is based on data from CA180-372 (NCT01460160), a Phase 2 trial which evaluated the addition of Sprycel to a chemotherapy regimen modeled on a Berlin-Frankfurt-Munster high-risk backbone in pediatric patients with newly diagnosed Ph+ ALL.
European Commission Approves ADCETRIS® (brentuximab vedotin) with AVD, the First New Treatment in Decades for Adults with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma [Takeda] ADCETRIS in Combination with AVD (Adriamycin, Vinblastine and Dacarbazine) Demonstrated 29-Percent Reduction in the Risk of Progression, Death or Need for Additional Anticancer Therapy for CD30+ Stage IV Patients.
Genmab Announces U.S. FDA Approval of DARZALEX® (daratumumab) Split Dosing Regimen [Genmab] The split dosing option was previously approved in Europe by the European Commission in December 2018.
	5.4 TRAITEMENTS - ECONOMIE
‘One-and-done’ for new drugs could cut patent thickets and boost generic competition [STAT] We should make the legal changes necessary to prevent companies from building patent walls and piling up mountains of rights. This could be accomplished by a “one-and-done” approach for patent protection.
	5.5 ASCO
Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) Demonstrates Continued Survival Benefit at 30-Month Follow-up in Patients with Previously Untreated Advanced or Metastatic Renal Cell Carcinoma [BMS] “The results from this 30-month follow-up from the CheckMate -214 study are meaningful as they continue to demonstrate that in patients with advanced renal cell carcinoma, a population with considerable unmet treatment needs, there is potential for long-term survival benefits with the combination of nivolumab and ipilimumab,” said CheckMate -214 investigator Nizar M. Tannir.
Phase 3 ARCHES Trial Shows XTANDI® (enzalutamide) Significantly Improved Radiographic Progression-Free Survival in Men with Metastatic Hormone-Sensitive Prostate Cancer [Pfizer] Data to be presented at the 2019 Genitourinary Cancers Symposium.
Pembrolizumab Plus Axitinib Extended Overall Survival and Progression-Free Survival Versus Current Standard Treatment for Advanced Kidney Cancer [ASCO] “We have a number of unanswered questions at this point, particularly the absence of biomarkers to predict response. PD-L1 levels, which have been markers for immunotherapy success in other cancers, remain unproven in renal cancer. It is possible that by combining pembrolizumab with axitinib, the predictive value of PD-L1 is being masked.”
African-American Men With Advanced Prostate Cancer Live Longer Compared With White Men When Treated With Newer Hormone Therapies [ASCO] After adjusting for demographic and clinical characteristics available in the VHA database, researchers found that African-American men treated with either hormone therapy lived for a median of 30 months, compared with 26 months for white men.
Merck Highlights Breadth of Immuno-Oncology Research Program in Genitourinary Cancers at ASCO GU [Merck] First-Time Data from Pivotal Phase 3 KEYNOTE-426 Trial Showing KEYTRUDA ® (pembrolizumab) in Combination with Inlyta ® (axitinib) Significantly Improved OS, PFS and ORR Compared to Sunitinib Monotherapy in First-Line Treatment of Advanced Renal Cell Carcinoma. Three New KEYTRUDA Combination Datasets from the Largest Study of Anti-PD-1 Therapy in Metastatic Prostate Cancer (KEYNOTE-365).
Phase II Trial Shows Novel, Radiolabeled PSMA-Targeted Treatment Provides High Response Rates in Men With Metastatic Prostate Cancer [ASCO] According to the researchers, men receiving the medication lived a median of 13.3 months after treatment, longer than the average 9-month survival time for men with this stage of disease.
Merck, Pfizer combo treatment boosts kidney cancer survival [Reuters] Approval of the combination to treat patients with RCC would put Merck again in competition with rival Bristol-Myers Squibb Co’s Opdivo, which is already being used in combination with another Bristol-Myers drug, Yervoy, to treat kidney cancer.
	6. LUTTE CONTRE LES CANCERS
Europe’s next €1-billion science projects: six teams make it to final round [Nature] The six newly shortlisted initiatives include: a project that would explore how AI can enhance human capabilities; one to hasten clinical availability of cell and gene therapies; a personalized-medicine initiative; two projects that aim to make solar energy more efficient; and a humanities project called the Time Machine, which seeks to develop methods for enabling digital search of historical records in European cities.
	6.3 ASSOCIATIONS/FONDATIONS
A Man On A Mission: How One Patient Journey Can Change The Course Of A Hereditary Cancer [Forbes] While AliveAndKickn continue to build their own registry and work on future endeavors like an app for Lynch syndrome patients and care givers to navigate their own journeys before, during, and after diagnosis, the Dubin family continues their own personal mission to fight the hereditary syndrome.
	6.6 PUBLICATIONS
Taking Stock of the Feedback on Plan S Implementation Guidance [The Scholarly Kitchen] There is enthusiasm and support for the overall goals of Plan S; however, there is also a great deal of concern about the implementation guidance and the very real possibility of negative unintended effects.
	6.7 DMP, BIG DATA & APPLIS
Technology and humanity in healthcare: the Topol Review [PHG Foundation] Several important assumptions are made throughout the Review, notably that whilst there is ‘remarkable potential’ for digital healthcare technologies (a blanket term used to include genomics, wearables and sensors, AI and apps, robotics, virtual and augmented reality, and more) to improve quality and efficiency of care, ‘implementation must only be carried out when there has been robust clinical validation’.
	6.7.1 IA/BIOINFORMATIQUE
A.I. Shows Promise as a Physician Assistant [NY Times] “Medicine is a slow-moving field,” said Ben Shickel, a researcher at the University of Florida who specializes in the use of deep learning for health care. “No one is just going to deploy one of these techniques without rigorous testing that shows exactly what is going on.”
	6.7.2 APPLIS
Apple to Deploy Health Records Feature on iPhone to Veterans [HIT Consultant] Health Records on iPhone will be the first record-sharing platform of its kind available to the VA, which is the largest medical system in the United States providing service to more than 9 million veterans across 1,243 facilities.