Onco Actu du 14 mai 2018

	1. Biologie
Adaptive Oncogenesis: How Cancer Evolves inside Us by James DeGregori [EvMed Review] Just out from Harvard University Press, DeGregori's book takes a sophisticated ecological perspective on cancer evolution within the body, and the dramatic clinical implications. The reviews below give a flavor for the advances he describes and extends. Highly recommended.
	3.1 Prévention - Tabac
Thirdhand smoke is widespread and may be dangerous, mounting evidence shows [Washington Post] The latest study, published Wednesday in the journal Science Advances, shows how tobacco smoke from outdoor air can seep into a nonsmoking classroom and coat its surfaces, and how those hazardous chemicals often become airborne again and circulate throughout buildings via central air-conditioning systems.
	3.1.1 Prévention - Tabac - e-cigs
The Promise of Vaping and the Rise of Juul [The New Yorker] Teens have taken a technology that was supposed to help grownups stop smoking and invented a new kind of bad habit, molded in their own image.
	3.3 Prévention - Vaccins
Journal retracts paper claiming neurological damage from HPV vaccine [Science] Scientific Reports this morning retracted a controversial paper claiming to show that mice given a human papillomavirus (HPV) vaccine showed signs of neurological damage. The paper was assailed by critics as being "pseudoscience" that could have "devastating" health consequences by undermining public confidence in a vaccine given to girls to prevent cervical cancer.
Does HPV vaccination prevent the development of cervical cancer? Are there harms associated with being vaccinated? [Cochrane] A team of Cochrane researchers has summarized results of 26 studies in 73,428 women conducted across all continents over the last eight years.
Major review backs cervical cancer shots, especially for teens [Reuters] The research by scientists at the respected scientific network the Cochrane Review also found no increase in the risk of serious side effects, with rates of around 7 percent reported by both HPV-vaccinated and control groups.
HPV vaccine 'safe and effective', says review [NHS Choices] HPV vaccination has been shown in this study to reduce the chances of women getting pre-cancerous cells in the cervix, but we need to see longer-term results to be sure this translates into a reduced chance of cervical cancer.
	3.6 Prévention - Activité physique
Vigorous exercise reduces tiredness in testicular cancer survivors [Cancer Research UK] Researchers invited 63 testicular cancer survivors to take part in a 12-week exercise programme which included repeatedly walking fast uphill on a treadmill set at an incline for two minutes and then at a slower pace on the flat for the same length of time.
Cancer: 'If exercise was a pill it would be prescribed to every patient' [The Guardian] Leading Australian researchers back world-first campaign for activity to be part of any treatment.
	3.7 Prévention - Alcool
Warning drinkers of cancer risk could reduce consumption, survey finds [The Guardian] Drinkers were asked to read a number of advisory messages and say which might persuade them to drink less.
	3.8 Prévention - Alimentation
Cancer warnings to be served up with coffee in California [Reuters] Superior Court Judge Elihu Berle in a ruling published on Monday said that Starbucks and other coffee sellers did not show that the risk from consuming acrylamide, a possible cancer-causing byproduct created during coffee roasting, was offset by benefits from drinking coffee.
	4.1 Dép., diag. & prono. - Prostate
The Pendulum Swings (Back) on Prostate Cancer Screening [ACS] Still, every man accepting screening should realize that along with a chance of benefit, there is a chance of harm; a high rate of false positives, a high chance of having a prostate biopsy, and the inconveniences and side effects associated with those are essentially exchanged for a relatively small chance of one’s life being saved.
Prostate cancer diagnosis: how scientists are working to get it right [Cancer Research UK] Specialist MRI to guide biopsies looks like a big step forward. But what if it could replace biopsies altogether? That’s what Emberton and his team are aiming to find out, in a new study funded by the Medical Research Council and Cancer Research UK.
Prostate cancer screening test is overused for older men, experts say [The Guardian] Overuse of the PSA test can lead to painful and unnecessary biopsies as well as over-diagnosis and over-treatment.
Experts have new advice on prostate cancer screening. Here's why they put it back on the table [LA Times] The task force cautioned, however, that there is insufficient evidence on the role of race and family medical history to draft separate recommendations for subgroups.
Implications of the New USPSTF Prostate Cancer Screening Recommendation—Attaining Equipoise [JAMA Internal Medicine] By now supporting individualized decision making, the USPSTF implies an equipoise where a small net benefit in reducing the risk of prostate cancer death for some men must be balanced against the more likely potential of experiencing non–life-threatening harms.
Prostate cancer screening: the decision is up to you [Reuters] For men aged 70 years and older, USPSTF discourages prostate cancer screening, because it has shown no benefit on prostate cancer-related death rates in this age group.
US panel leaves prostate screening up to men, their doctors [AP] The guidance says it’s important to weigh the potential benefits and harms of screening. The test looks for elevated levels of a protein in the blood that may signal cancer but can also be caused by less serious prostate problems.
	4.2 Dép., diag. & prono. - Génome
Protecting confidentiality in genomic studies [MIT News] In a paper appearing today in Nature Biotechnology, researchers from MIT and Stanford University present a new system for protecting the privacy of people who contribute their genomic data to large-scale biomedical studies.
	4.5 Dép., diag. & prono. - Colorectal
Society for Immunotherapy of Cancer (SITC)-Led Study Demonstrating Prognostic Power of “Immunoscore” Published in The Lancet [SITC] The findings of this large-scale study showed that stage I-III colon cancer patients’ Immunoscores are positively correlated with survival as well as the “time to recurrence” of cancer.
	4.9 Dép., diag. & prono. - Sein
Screening Mammography Lowers Breast Cancer Patients' Needs For Aggressive Treatment, Study Finds [Forbes] What’s great about this work, in my view, is that it opens the door to more studies of screening women in their forties.
Regular Mammograms Mean Earlier Breast Cancer Diagnosis and Less Aggressive Treatment [American Society of Breast Surgeons] A study of more than 1,000 breast cancer patients found that those who had a mammogram within 24 months of diagnosis had smaller tumors and were less likely to have been treated with mastectomy, chemotherapy and axillary node dissection than those who did not.
Breast screening error: women need reassurance, not misleading statistics [Cancer Research UK] But even then, it may be hard to find out what might have happened had this failure not taken place. In part because it is incredibly difficult to unpick what could have happened to each individual woman, as well as the difficulty in pinning down the precise benefits that final breast screening appointment may offer.
Breast cancer screening programme 'does more harm than good' [BBC News] In the letter to the newspaper, the group of academics and GPs say women aged 70-79 who are being offered catch-up appointments should only seek help if they notice a lump or other symptoms.
Can we say who has died because of the breast-screening appointment error? [University of Cambridge] These are ‘statistical’ harms — I don’t see how it will be possible to say with any confidence that any particular individual has died because of this error. For newspapers (or lawyers) to suggest otherwise only seems to make a bad situation even worse.
Breast cancer screening hotline staffed by people with only an hour's training [The Guardian] Staff said the rush to set up the hotline led them to fear mistakes could be made in the handling of women’s cases as they were not medical professionals and had received so little training.
Breast cancer screening scandal must prompt review of mammograms [The Guardian] Doctors and patients should be fully informed about the true balance of risks and benefits.
	5. Traitements
Most Oncologists Have Discussed Medical Marijuana With Patients [ASCO] Survey Shows Patients With Cancer Initiate Conversations About Medical Marijuana, but Knowledge Gaps Persist.
	5.10 Traitements - Essais
When will clinical trials finally reflect diversity? [Nature] An analysis of drug studies shows that most participants are white, even though trials are being done in more countries.
	5.12.1 Immunothérapies - partenariats
Medigene in for up to $1.5 billion under broader pact with Bluebird Bio [Reuters] The number of projects in the alliance, which has Medigene contributing screening tools to identify promising T-cell receptors (TCR), will rise from four to six, Medigene said in a statement on Monday, sending its shares 8 percent higher.
Merck and OncoSec expand Keytruda/IL-12 collaboration into triple-negative breast cancer [FierceBiotech] The phase 2 trial will evaluate Merck’s anti-PD-1 therapy Keytruda (pembrolizumab) and OncoSec’s ImmunoPulse IL-12 in patients with locally advanced and inoperable or metastatic disease, following the failure of systemic chemotherapy or an immunotherapy.
	5.12.10 Immunothérapies - Fusions et acquisitions
Playing catch-up, Eli Lilly swoops in with $1.6B cash deal for Armo Bio and its promising PhIII cancer drug [EndPoints] The lead drug is designed to spur the proliferation of CD8+ T cells in patients, improving prognosis and lengthening the survival of cancer patients.
	5.12.2 Immunothérapies - CAR-T
Belldegrun's Allogene looks to poach veteran biotech analyst for CFO: Stat [FierceBiotech] At Kite, Belldegrun and Chang ushered the first CAR-T treatment for non-Hodgkin lymphoma to an early FDA nod, eventually selling off the company to Gilead for nearly $12 billion. But making history wasn't enough for the duo, who launched Allogene in April with a mission to advance a stable of allogenic, or off-the-shelf, CAR-T candidates licensed from Pfizer.
Controlling CAR-T: How scientists plan to make the engineered T cell therapy safer, and work for more cancers [CEN] A growing number of biotech companies and researchers are devising control systems to make new CAR-T therapies simultaneously safer and more powerful. Installing emergency off switches, adding drug-controlled dials to tune T-cell activity, and building more selective sensors are all in development. Call it CAR-T 2.0.
	5.12.3 Immunothérapies-combinaisons
Roche-Exelixis Study Fails as Mixed Year Continues For Cancer Drug Combos [Xconomy] Roche and its South San Francisco-based Genentech unit appeared to blame the failure on the fact that 95 percent of the patients in the trial had microsatellite stable tumors.
Setback to Roche hopes for Tecentriq as fails key cancer trial [Reuters] Barclays Capital analysts, who rate Roche shares “overweight”, called the failure a disappointment but said CRC was always seen as a higher-risk opportunity, with only modest expectations of the indication adding significantly to sales.
Genentech Provides Update on Phase III Study Of TECENTRIQ (Atezolizumab) and COTELLIC (Cobimetinib) in People With Heavily Pre-Treated Locally Advanced or Metastatic Colorectal Cancer [Genentech] The results from IMblaze370 were consistent with this prior monotherapy experience, showing that treatment with TECENTRIQ alone did not provide a meaningful clinical benefit compared to regorafenib in this patient population.
A promising new cancer drug has hit a major setback, raising questions about whether the field is moving too fast [Science] A year ago, the future of IDO inhibitors looked bright. At the June 2017 meeting of the American Society of Clinical Oncology, doctors reported that epacadostat, given with the approved checkpoint inhibitor Opdivo, shrank tumors in 25 of 40 of melanoma patients—roughly double the historical response rate of Opdivo alone.
	5.12.5 Immunothérapies - Pharma
FDA grants priority review to Roche’s cancer immunotherapy TECENTRIQ (atezolizumab) for initial treatment of people with a specific type of metastatic lung cancer [Roche] The FDA is expected to make a decision on approval by 5 September 2018.
Roche's Tecentriq combo wins fast FDA review in race to catch rivals [Reuters] Tecentriq’s status as a late-comer in immunotherapy compared to Keytruda and Bristol-Myers Squibb’s Opdivo has contributed to sluggish sales.
FDA promises Roche a snap decision on Tecentriq triple for frontline lung cancer as it falls even further behind Merck, Bristol-Myers [EndPoints] Roche is getting some help from the FDA in its quest to start making up some of the multibillion-dollar distance that separates the global player from Merck and Bristol-Myers Squibb in the blockbuster rivalry over the lung cancer market.
	5.12.8 Immunothérapies - Economie
Why did Merck issue an unusual press release? It knows investors are hyperfocused on I-O data [FiercePharma] But beyond hinting at Merck’s hand, the move illustrated the pressure on companies—immuno-oncology drugmakers in particular—that’s coming from shareholders, who are monitoring the I-O landscape like hawks and have been known to let fears run wild and run down a stock based on a false premise.
	5.2 Pharma
Daiichi Sankyo in pursuit of Novartis’ Rydapt with next-generation FLT3 drug [FierceBiotech] The data from the QuANTUM-R isn’t available to view just yet, but Daiichi Sankyo has said it can move ahead with regulatory filings for quizartinib as a second-line option for AML.
	5.2.1 Pharma - Partenariats
Flatiron, BMS form collaboration to curate regulatory-grade real-world data [The Cancer Letter] Flatiron continues to maintain autonomy in its partnerships, and the Roche acquisition does not present a conflict of interest for the company or Roche’s competitors, Abernethy said.
BMS’s Saha: We’re at the start of defining new endpoints, hypotheses with real-world evidence [The Cancer Letter] Digital health is a very core capability that we’re incorporating across most functions of the company, and our work with Flatiron is certainly a part of those efforts.
	5.2.2 Pharma - Fusions & Acquisitions
Takeda to vault into Big Pharma with $62B Shire buyout—and megamerger cuts are on the way [FierceBiotech] Most of the cuts will hit SG&A, thanks to the two companies' overlapping operations in their gastrointestinal and neuroscience businesses, Welford said. Another 43% will come from R&D—about $600 million—mostly from removing "duplicate costs."
Proposed Acquisition of Shire plc by Takeda [Takeda] With leading market positions in prioritized therapeutic areas, an attractive geographic footprint, greater scale and efficiencies, and an even more productive R&D engine, the combined group will be better positioned to deliver highly-innovative medicines and transformative care providing better health and a brighter future for patients around the world.
Takeda CEO Christophe Weber finally closes on his $62B deal to buy Shire — now he has to convince shareholders and slash jobs [EndPoints] Drill down into the fine print of the deal, and you’ll find that the top execs at Takeda will ax 6% to 7% of the combined workforce. About a third of that will come out of R&D, with the bulk of the cuts being made to sales and administration.
	5.2.3 Pharma - économie
Democratic senator opens probe into Novartis over its dealings with Trump’s attorney [STAT] In any event, the contract with Cohen has caused Novartis considerable grief.
Essential Consultants – Novartis statement [Novartis] With the recent change in administration, Novartis believed that Michael Cohen could advise the company as to how the Trump administration might approach certain US healthcare policy matters, including the Affordable Care Act.
Novartis paid Trump’s lawyer’s firm far more than any of its actual lobbyists [STAT] Asked about the difference between the payments to Cohen’s company and those listed in the lobbying records, a Novartis spokesman said, “[I] really don’t have an answer to that one.”
Novartis paid nearly $400,000 to a shell company controlled by Trump’s attorney [STAT] A Novartis unit called Novartis Investment SARL made four payments, each one totaling $99,980, to the consulting firm, according to documents released by Michael Avenatti, the lawyer for Stormy Daniels, the pornographic film star whose real name is Stephanie Clifford and who was paid $130,000 by Essential Consultants to keep quiet about her alleged affair with Trump.
	5.3 Traitements - FDA, EMA, NICE...
Two years of PRIME [EMA] The report, published today, presents results from the first two years of PRIME. It explains how the criteria for eligibility to the scheme have been applied and what type of support applicants have received so far.
Gottlieb pushes back against criticism of ‘breakthrough’ designation [STAT] “I’ve seen some of what you perceive as criticism,” Gottlieb said in response to a question about the program at the annual meeting of the Reagan-Udall Foundation for the FDA, a nonprofit created by Congress to support the activity of the agency. “I perceive it as healthy dialogue.”
	5.3.4 Traitements - AMM (FDA, EMA,...)
LYNPARZA® (olaparib) Tablets Receive EU Approval for the Treatment of Platinum-Sensitive Relapsed Ovarian Cancer [Merck] The EU approval was based on two randomized trials, SOLO-2 and Study 19, which showed that LYNPARZA reduced the risk of disease progression or death for platinum-sensitive relapsed ovarian cancer patients compared to placebo.
FDA Approves Nivolumab and Ipilimumab Combination for Advanced Kidney Cancer [NCI] This is the first immunotherapy regimen to be approved by FDA for the initial treatment of patients with kidney cancer.
Janssen Announces DARZALEX® (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible [Janssen] The FDA approval of DARZALEX® in combination with VMP is supported by data from the randomized, open-label, multicenter Phase 3 ALCYONE (MMY3007) study, recently published in the New England Journal of Medicine.
EMA Recommends Approval of Generic Carmustine [ESMO] It is indicated for the treatment of brain tumours, non-Hodgkin’s lymphoma and Hodgkin’s disease.
FDA approves new uses for two drugs administered together for the treatment of BRAF-positive anaplastic thyroid cancer [FDA] The trial measured the percent of patients with a complete or partial reduction in tumor size (overall response rate). Of 23 evaluable patients, 57 percent experienced a partial response and 4 percent experienced a complete response; in nine (64 percent) of the 14 patients with responses, there were no significant tumor growths for six months or longer.
Rucaparib Approved as Maintenance Treatment for Some Recurrent Ovarian Cancers [NCI] Overall, the women who received rucaparib had a longer time before their disease progressed (progression-free survival) than women in the placebo group: 10.8 months, compared with 5.4 months.
	5.4 Traitements - Economie
Long term benefit of neuroblastoma treatment is too uncertain, says NICE [NICE] NICE has published draft guidance in which dinutuximab beta is not recommended as a treatment for high-risk neuroblastoma – a rare type of cancer that mainly affects children and young people.
Hundreds of people with blood cancer given more treatment options after NICE recommends three drugs [NICE] NICE has recommended three blood cancer drugs, brentuximab vedotin, midostaurin and arsenic trioxide be made available on the NHS.
	5.5.1.1 ASCO (général) - Industriels
Roche to present new data from its industry-leading oncology portfolio at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting [Roche] More than 180 abstracts have been accepted across 13 cancer types, including two “late breakers” and 15 oral presentations.
	6. Lutte contre les cancers
"All of us" Who are 'us'? [Memaid's Tale] Every lock on Big Money for the Big Data lobby, or perhaps belief-system, excludes funding for focused research, for example, on diseases that would seem to be tractably understood by real science rather than a massive hypothesis-free fishing expedition.
Pay it forward: Join with All of Us Research Program to build a healthier future [USA Today] Over the past year, All of Us has already carried out an early testing phase. More than 27,000 pioneering participants have enrolled. The All of Us pilot phase is already as big as the entire Framingham study!
The NIH Launches Its Ambitious Million-Person Genetic Survey [Wired] Building out the infrastructure necessary to collect so much data on such a huge cohort has taken time and some serious cash.
	6.10.1 Politiques (USA)
Trump promised to bring pharma to justice. His speech sent drug stocks soaring [STAT] The stock prices of Pfizer, Merck, Gilead Sciences, and Amgen all spiked after Trump’s speech.
Statement from FDA Commissioner Scott Gottlieb, M.D., on the Trump Administration’s plan to lower drug prices [FDA] The President made it clear today that we all need to play a role—including the FDA and its sister agencies like the Centers for Medicare & Medicaid Services—to put American patients first by taking bold actions to help patients have access to affordable medicine.
No big surprises for pharma in Trump's speech. President's plan 'very, very positive' for the industry, analyst says [FiercePharma] While many of the Trump Administration's proposals have been discussed before, officials did suggest at least one novel idea. Department of Health and Human Services secretary Alex Azar said drugmakers should have to disclose pharmaceutical prices on ads, giving consumers more information and changing pharma's pricing incentives at the same time.
Trump Drug Pricing 'Blueprint' Could Take Years To Build [NPR] The 39-page drug price plan includes an array of ideas that the administration will consider, but it's unclear which ones will be implemented.
Trump’s ‘sweeping action’ to lower drug prices mocked by analysts as relieved investors trigger rally in Big Pharma stocks [EndPoints] What we heard about today amounted to some tailoring and planned slimming — the basic outfit remains the same. And that fact helped trigger a broad rally in Big Pharma stocks after the speech wrapped.
Trump assails high drug prices, avoids direct hit on industry [Reuters] Trump also placed blame on foreign governments, saying they “extort unreasonably low prices” from U.S. drugmakers, forcing companies to charge more in this country.
Trump Promises Lower Drug Prices, but Drops Populist Solutions [NY Times] Speaking in the sun-splashed Rose Garden of the White House, Mr. Trump said that a “tangled web of special interests” had conspired to keep drug prices high at the expense of American consumers.
What’s Good for Pharma Isn’t Good for America (Wonkish) [NY Times] Yes, Trump says he wants to force other countries to raise drug prices. Good luck on that. What this comes down to is that there is a very strong case for doing what Trump promised to do but didn’t.
	6.11 Patients
Through my cancer, I have found the key to a good life [The Guardian] Prostate cancer surgery is no fun. But in two months I’ve learned more about myself and the world than in the previous two decades.
	6.4 Médico-éco
Women With Breast Cancer Delay Care When Faced With High Deductibles [NY Times] When Pam Leonard felt a lump in her breast last November, she hesitated, debating whether to get testing to see if she had cancer. She thought of her insurance policy, which carries a deductible of $2,600. She knew she would also have to spend as much as $5,700 on medical bills that would not be covered by an individual policy she bought under the Affordable Care Act.
	6.7 DMP, Big Data & applis
Will Real World Performance Replace RCTs As Healthcare's Most Important Standard? [Forbes] Thus far, we’ve considered robust RWE as a somewhat imperfect alternative to the scientific gold standard, RCT. But if you take a step back, you might ask why this benchmark takes priority over what may be a more relevant standard – how a product performs in the real world.
	6.9 Controverses
Basic scientists still feel pinch of new NIH clinical trial policy [Science] The clinical trial policies “are not appropriate for fundamental research,” a group of societies wrote in an email to NIH this week. The issue goes back almost a year, when researchers became aware that a new NIH definition of clinical trials would encompass many basic studies involving human subjects.
Digital Photocopiers Loaded With Secrets [CBS] It wasn't until hitting "print" on the fourth machine - from Affinity Health Plan, a New York insurance company, that we obtained the most disturbing documents: 300 pages of individual medical records. They included everything from drug prescriptions, to blood test results, to a cancer diagnosis.