Onco Actu du 2 mai 2018

	1. Biologie
Cryo-EM Images Capture Key Enzyme Tied to Cancer, Aging [NIH Director's Blog] This structural biology advance is a critical step toward learning more about the role of telomerase in cancers, as well as genetic conditions linked to telomerase deficiencies. It’s also an important milestone in the quest for drugs targeting telomerase in different ways, perhaps to slow the growth of cancerous cells or to boost the proliferative capacity of life-giving adult stem cells.
	3.1.1 Prévention - Tabac - e-cigs
FDA, FTC take action against companies misleading kids with e-liquids that resemble children’s juice boxes, candies and cookies [FDA] Warning letters are part of joint effort to protect youth from dangers of nicotine and tobacco products and part of FDA’s new Youth Tobacco Prevention Plan.
Liquid nicotine for e-cigs looks like kids’ juice boxes and candy, government says [Washington Post] Federal regulators warned Tuesday that more than a dozen manufacturers, distributors and retailers that they are endangering children by marketing e-cigarette liquids to resemble kid-friendly products such as juice boxes, candy and whipped cream.
	3.3 Prévention - Vaccins
Doctors paying for sons to have cancer jab [BBC News] "Lots of doctors are having their boys vaccinated because they can afford it, as are those who are better informed," he said. "But what about those who can't afford it? Cases of throat cancer are soaring. It's indefensible.
	4. Dépistage, diagnostic et pronostic
Moving Beyond BMI: Low Muscle Mass May Affect Cancer Survival [NCI] Body surface area is “a crude measure,” he continued. “It’s more than 100 years old.” Using CT scans to differentiate adiposity and muscle mass may eventually “help to inform dosing decisions,” he said.
	4.2 Dép., diag. & prono. - Génome
Cracking the Code of Life—at Light Speed [Wall Street Journal] Mike Hunkapiller helped invent the DNA-sequencing machines that read the human genome. Now his company’s tools are decoding everything from insects to cancer cells.
	4.9 Dép., diag. & prono. - Sein
New approach for hard-to-treat BRCA breast cancer shrinks tumours twice as fast [The Telegraph] The results are likely to change international guidelines by introducing genetic testing for women with triple-negative breast cancer.
Gene test might benefit women with hard-to-treat breast cancer [Cancer Research UK] “Rather than offering all women the same standard of care, these results show that, for patients with inherited BRCA mutations, the drug carboplatin is not only a more effective treatment option, but also comes with fewer side effects, sparing patients possible health problems, physical discomfort and emotional distress.”
	5. Traitements
Poziotinib as a Clinically Active Inhibitor of EGFR and HER2 exon 20 mutations [ESMO] In a phase II trial, the first 11 patients with NSCLC with EGFR exon 20 mutations receiving poziotinib had a confirmed objective response rate of 64%.
	5.10 Traitements - Essais
Unreported clinical trial of the week: Temsirolimus and Bevacizumab for cancer patients (NCT01010126) [BMJ] This unreported trial was sponsored by the National Cancer Institute and funded under 17 separate NCI grant contracts.
	5.12.1 Immunothérapies - partenariats
George Church, CRISPR Pioneer, Embraces Alternative Tech In Project To Recode A Human Genome [Forbes] If it worked, the cells might be used in manufacturing or to create cancer-killing white blood cells of the type that Cellectis is developing. But the implication would be even bigger: it would mean that in the future DNA might be far more changeable than just about anyone imagines now.
Harvard's Wyss Institute partners with Cellectis to recode the human genome [PR Newswire] Recode project will use Cellectis' TALEN gene editing technology to create first virus-resistant human cells for manufacturing therapeutics and developing new cell-based therapies.
	5.12.2 Immunothérapies - CAR-T
SUPRA CAR T cell system provides more of cosmetic rather than a real advance [NIHilist's Immunology] First, none of those above mentioned three advantages were actually shown for tumor models in vivo. Moreover, in vitro experiments showing decoy effect was done in manner that is incompatible for in vivo experiments.
	5.12.3 Immunothérapies-combinaisons
Incyte wipes out late-phase epacadostat program after pivotal failure of Keytruda combination [FierceBiotech] Incyte’s reorganization of its portfolio of trials amounts to a major, although not quite total, retreat from epacadostat. A pair of studies of epacadostat and Keytruda in non-small cell lung cancer (NSCLC) that started late last year will continue as phase 2 trials, not the pivotal programs originally envisaged.
IDO Appears to Have Wiped Out [In the Pipeline] So I think we can say that (at least as currently configured) the excursion into IDO inhibitors has been a costly mistake. And remember, as is almost always the case in these things, that it didn’t look like it was going to be any such thing.
Bristol-Myers Latest to Drop IDO Studies in Wake of Incyte Failure [Xconomy] Soon after that disclosure, NewLink Genetics of Ames, IA, said it would curtail a Phase 3 combination study of its IDO inhibitor indoximod for melanoma “in the context of the failure of a competitor’s trial.”
IDO rout: Pivotal trials with Bristol-Myers, Merck and AstraZeneca dumped in wake of Incyte’s PhIII implosion [EndPoints] In the wake of a pivotal failure of Incyte’s lead IDO drug epacadostat, Bristol-Myers Squibb has become the third player forced to retrench in that immuno-oncology field, dropping three late-stage studies of a rival drug it bagged in a $1.25 billion buyout.
	5.12.5 Immunothérapies - Pharma
Leena Gandhi steps out of Keytruda spotlight and into a top research job at I/O laggard Eli Lilly [EndPoints] Two weeks ago, Leena Gandhi was in the spotlight at AACR with the latest landmark data on Merck’s Keytruda/chemo combo for frontline lung cancer. Today, we find out that Gandhi, an investigator at the Perlmutter Cancer Center at NYU Langone Health and a Dana-Farber vet, has been recruited by none other than Eli Lilly to head up its immuno-oncology research work.
	5.12.6 Immunothérapies - AMM
Kymriah® (tisagenlecleucel), first-in-class CAR-T therapy from Novartis, receives second FDA approval to treat appropriate r/r patients with large B-cell lymphoma [Novartis] Kymriah demonstrated an overall response rate of 50%, with median duration of response not yet reached at the time of data cut-off, indicating sustainability of response.
U.S. approves Novartis cell therapy for lymphoma [Reuters] The new indication puts Kymriah in direct competition with Gilead Sciences’ Yescarta, which was approved by the U.S. Food and Drug Administration in October for treatment of adults with diffuse large B-cell lymphoma who have failed to respond to other treatments.
Kymriah wins second FDA OK, boosting hope for Novartis’ low CAR-T sales [EndPoints] Kymriah — the first CAR-T ever to get approval — is now also the first CAR-T to get approval for two distinct indications in non-Hodgkin lymphoma (NHL) and B-cell ALL.
	5.12.8 Immunothérapies - Economie
Merck’s Dangerous Keytruda Success [Bloomberg] By 2022, analysts expect Keytruda to account for at least a quarter of Merck’s total sales and the vast majority of its sales growth.
	5.2 Pharma
Karyopharm to pursue FDA approval for multiple myeloma drug based on new study results [STAT] The small biotech announced Monday evening that 25 percent of multiple myeloma patients responded to treatment with selinexor in a single-arm clinical trial. The median duration of response was 4.4 months.
Karyopharm stock soars on selinexor’s positive PhIIb update, plans for an NDA [EndPoints] The Newton, MA-based biotech plans to submit an NDA to US regulators during the second half of 2018, along with an application to the EMA in early 2019.
	5.2.3 Pharma - économie
Pfizer first-quarter results miss estimates as key drug sales fall short [Reuters] The company said that Ibrance had raked in sales of $933 million in the first quarter, up 37.4 percent from a year earlier but missing analysts’ estimates of $956.6 million.
	5.3.4 Traitements - AMM (FDA, EMA,...)
Tagrisso receives positive EU CHMP opinion for 1st-line treatment of EGFR-mutated non-small cell lung cancer [AstraZeneca] Recommendation based on FLAURA trial data showing unprecedented median progression-free survival of 18.9 months for Tagrisso versus 10.2 months compared with current standard of care.
Novartis receives FDA approval of Tafinlar® + Mekinist® for adjuvant treatment of BRAF V600-mutant melanoma [Novartis] Tafinlar + Mekinist is the first oral targeted adjuvant combination therapy to demonstrate significant clinical benefit in patients with a BRAF V600 mutation, following complete surgical resection.
Amgen Receives Positive CHMP Opinion To Add Overall Survival Results From The Phase 3 ASPIRE Study To KYPROLIS® (carfilzomib) Label [Amgen] KYPROLIS is the First and Only Relapsed or Refractory Multiple Myeloma Treatment to Demonstrate Overall Survival in two Phase 3 Studies.
CHMP recommends EU approval of Roche’s Perjeta for post-surgery treatment of HER2-positive early breast cancer at high risk of recurrence [Roche] In the large phase III APHINITY study, the combination of Perjeta, Herceptin and chemotherapy significantly reduced the risk of invasive breast cancer recurrence or death by 19% compared to Herceptin and chemotherapy alone in the overall study population.
Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 23-26 April 2018 [EMA] The Committee recommended extensions of indications for Cimzia, Perjeta, Prolia, Sprycel, Tagrisso, Xeljanz, Xultophy and Yervoy.
EMA Recommends Extension of Indications for Pertuzumab [ESMO] Recommendation concerns the neoadjuvant and adjuvant treatment of HER2-positive early breast cancer at high risk of recurrence.
EMA Recommends Extension of Indications for Osimertinib [ESMO] New indication concerns first-line treatment of adult patients with locally advanced or metastatic NSCLC with activating EGFR mutations.
FDA approves dabrafenib plus trametinib for adjuvant treatment of melanoma with BRAF V600E or V600K mutations [FDA] Approval was based on COMBI-AD (NCT01682083), an international, multi-center, randomized, double-blind, placebo-controlled trial in 870 patients with Stage III melanoma with BRAF V600E or V600K mutations, and pathologic involvement of regional lymph node(s).
	5.4 Traitements - Economie
China to cut import value-added tax on cancer drugs from May 1 [Reuters] The government has said it would remove import tariffs on cancer drugs from next month.
Value-Based Pricing for Drugs [JAMA] The term value-based pricing has been redefined beyond its original meaning, and now constitutes shorthand for any change to traditional payment models for drugs, regardless of the underlying approach to determining the final price of the product.
	5.9.1 AACR - sein
PARP Drugs Help Some Breast Cancer Patients, But They're No Magic Bullet [Forbes] In the room at McCormick Place where Dr. Robson presented the data at the AACR meeting, I sensed disappointment on the part of investigators and others even among doctors who run trials of competing drugs for metastatic breast cancer.
	5.9.4 AACR - poumon
Immunotherapy Drugs Expand Treatment Options for Advanced Lung Cancer [NCI] "This study represents a total change in the way we approach the treatment of patients with metastatic lung cancer," said the trial’s lead investigator, Leena Gandhi, M.D., Ph.D., of the Perlmutter Cancer Center at NYU Langone Health.
	6. Lutte contre les cancers
NIH opens nationwide enrollment for huge precision medicine initiative [STAT] The program, which began as a pilot last year, is the most ambitious attempt yet to compile health and behavioral data, as well as genetic sequencing, from a representative sample of the American population.
	6.1 Observation
Ovarian cancer diagnoses 'will rise 55% in the next 20 years' [The Guardian] Global coalition says more must be done to treat ovarian cancer, which has the lowest survival rate of all female cancers.
A rare eye cancer showed up in three friends. Doctors want to know if the cases are connected. [Washington Post] “Most people don’t know anyone with this disease,” Orloff said. “We said, 'Okay, these girls were in this location, they were all definitively diagnosed with this very rare cancer — what’s going on?’ ” Alabama health officials have declined to call the outbreak a cluster yet.
	6.3 Associations/Fondations
A better understanding of brain tumour biology will bring new treatments [Cancer Research UK] Today, at our inaugural Brain Tumour Conference in London, we’re announcing six research themes that we believe will help scientists focus on the gaps in knowledge about brain tumours. And there’s £18 million up for grabs for the best research ideas focused on these themes.
Cancer Research UK appoints new chief executive [Cancer Research UK] Michelle has been CEO of the MS Society since 2013. Under her leadership, there has been a 40% increase in access to effective MS treatments and she has developed a £100m research fundraising appeal.
Brain tumour research to get £18m injection [The Guardian] The new funding is part of a £25m boost in funding by CRUK for brain cancer research over the next five years, and is in addition to the £13m spent on the disease every year already by the charity.
	6.4 Médico-éco
For Cancer Centers, Proton Therapy’s Promise Is Undercut by Lagging Demand [NY Times] Proton therapy was initially used to treat tumors in delicate areas where surgery was not an option — near the eye, for example — and in children, and it remains the best choice in such cases. But its pinpoint precision has not been shown to be more effective against breast, prostate and other common cancers.
	6.5 Médecines alternatives
How is it that in 2018 cancer Stanislaw Burzynski is still preying on desperate cancer patients? [Respectful Insolence] Either way, Burzynski remains a cautionary tale of just how ineffectual the FDA and state medical boards can be when it comes to blatant quackery.
	6.7.1 IA/bioinformatique
Out to ‘rethink the drug design process,’ AI star Daphne Koller is creating a new machine learning venture at insitro with some heavyweight backers [EndPoints] To enable the machine learning, we will use high-quality data that has already been collected, but we will also invest heavily in the creation of our own datasets using high throughput experimental approaches, datasets that are designed explicitly with machine learning in mind from the very start.
	6.7.2 Applis
App turns smartphones into data crunchers to help find cancer treatment [The Telegraph] The app, launched by Vodafone, greatly reduces the time it takes to analyse the effect of various drug combinations against people with varying individual genetic makeups and send results back to researchers at Imperial College London.
Cancer researchers need phones to process data [BBC News] A cancer research team hopes to build a network of more than 100,000 UK smartphones to help process data while their owners sleep.
	6.8 Communication
Peter Tunney: How the largest art movement in history can help reduce cancer disparities [The Cancer Letter] Recently, Peter Tunney, an artist who runs two galleries in the Wynwood Walls Park in Miami, provided artwork to wrap an RV that Sylvester Comprehensive Cancer Center will use to take cancer interventions to Little Haiti, Liberty City, Little Havana and LGBTQ neighborhoods.
Miami’s Sylvester uses cool art to bridge disparities—and meet NCI’s new requirement [The Cancer Letter] The words “GAME CHANGER” were painted on the RV’s side, and if you looked closer, you saw the layering of iconic imagery of all things cancer. The van was a piece of moving art, a gigantic puppet, one artist’s contribution to the quest for social justice.