Onco Actu du 4 avril 2017

	1. Biologie
How understanding blood vessels and immunity could boost cancer treatment [FierceBiotech] Zhang and his team discovered that when they normalized the structure of blood vessels that feed breast tumors, they could encourage T cells to invade the tumors.
Hunt for cancer 'tipping point' heats up [Nature] 'Pre-cancer' genome atlas proposed to track tumours as they turn from benign to dangerous.
	2.11 Etiologie - Alimentation
Cancer warning over posh crisps as study shows they contain three times recommended levels of acrylamide [The Telegraph] The Food Standards Agency is also planning to extend the warning to every food-serving business in Britain. Under a new European Union food hygiene directive, due to be adopted in the UK by the the end of 2017, pubs and restaurants will be told to take reasonable steps to reduce acrylamide in food or face enforcement measures.
	4. Dépistage, diagnostic et pronostic
Tiny bubbles raise hope for biopsy-free cancer diagnosis [Stanford Medicine] In the technique, patients are intravenously injected with bubbles a little smaller than human red blood cells. The microbubbles, which are capable of latching onto the cancer cells but not healthy cells, sail through the blood vessels until they reach a malignant tumor, where they begin to accumulate in the blood vessels supplying the tumor.
	5. Traitements
Novocure's device-chemo combo boosts survival in pancreatic cancer [FierceBiotech] The prospective, single-arm PANOVA trial investigated the safety and efficacy of the company’s Tumor Treating Fields technology in combination with nab-paclitaxel and gemcitabine, according to a statement. It involved 20 pancreatic cancer patients whose tumors could not be surgically removed and who did not undergo chemotherapy or radiation therapy before the trial.
	5.12 Immunothérapies
Cancer researchers worry immunotherapy may hasten growth of tumors in some patients [STAT] Champiat said that he and his colleagues had mistakenly believed that patients whose cancer had entered a hyper-growth mode were merely experiencing pseudo-progression, so they continued the immunotherapy treatment. “We were probably deleterious because we maintained that,” he said.
	5.12.1 Immunothérapies - partenariats
Incyte Cancer Immunotherapy Drug Is Object of Desire for Two Big Pharma Rivals [The Street] The combination of two or immunotherapy drugs to treat cancer more effectively is the next big commercial opportunity. Bristol can't afford to lose any more ground, so it's shadowing Merck, move for move. And that suits Incyte just fine.
#AACR17: Fresh from Merck embrace, fast-growing Incyte pivots into a PhIII IDO1/Opdivo tie-up with Bristol-Myers [EndPoints] Ironically, Incyte emerges from these back-to-back deals continuing to be closely allied with the two top players in checkpoint inhibition.
	5.3 Traitements - FDA, EMA, NICE...
Collaboration with academia to be reinforced [EMA] EMA publishes framework and action plan for closer interaction.
Gottlieb as FDA commissioner would be music to pharma’s ears [STAT] Gottlieb has a long history of supporting deregulation of medical products.
Europe must find a new home for its drug regulator — and a way to keep using English [Nature] Various EU officials have already made it clear that the English language will not be allowed to exit the EU along with its main speakers on the continent — chaos would surely follow if, for example, the English-speaking EMA was expected to work with documents in every language but English.
	5.4 Traitements - Economie
Overcoming Challenges Of Outcomes-Based Contracting For Pharmaceuticals: Early Lessons From The Genentech–Priority Health Pilot [Health Affairs Blog] In 2015, Genentech(a drug manufacturer) and Priority Health (a nonprofit health plan) agreed to collaborate on an outcomes-based contract for Avastin ® (bevacizumab) in patients with non–small-cell lung cancer (NSCLC).
Strategies To Address The Challenges Of Outcomes-Based Pricing Agreements For Pharmaceuticals [Health Affairs Blog] Stakeholders frequently discuss outcomes-based pricing agreements (OBAs) as a promising alternative to traditional drug pricing strategies. These arrangements are a type of performance-based risk-sharing, in which prospective clinical outcomes data are used to link a drug’s price to its real-world efficacy.
The cost of cancer: new drugs show success at a steep price [Reuters] "Competition is key to lowering drug prices," Trump told pharmaceutical executives at an Oval Office meeting in January. But that is not happening with new drugs called checkpoint inhibitors.
	5.9 AACR
Stand Up To Cancer Names Top Researchers to $12 Million Dream Team on Colorectal Cancer [AACR] More than 50 researchers at six institutions are involved in the team.
Stand Up To Cancer Awards Innovative Research Grants in Immuno-oncology to 10 Early-career Scientists [AACR] Each grant worth $750,000 over three years.
“No Time to Stop the Momentum” [Cancer Research Catalyst] Biden offered a frank assessment of the political changes that have occurred since his first AACR appearance, when he addressed the audience at the Annual Meeting 2016 in New Orleans.
	5.9.1 AACR - sein
Triple-negative Breast Cancer Patients Who Responded to Immunotherapy Had Long-term Survival Benefit [AACR] A limitation is that the study did not have a randomized control group with standard therapy; the survival data could therefore only been seen in the context of historical controls, Schmid said.
	5.9.3 AACR - mélanome
Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) and Opdivo Monotherapy Significantly Improved Overall Survival Versus Yervoy Alone in Patients with Previously Untreated Advanced Melanoma [BMS] Safety profile is consistent with previous studies, with no cumulative toxicity with combination therapy or new safety signals.
Combination of Nivolumab and Ipilimumab Improved Overall Survival For Advanced Melanoma Patients [AACR] Larkin and colleagues enrolled 945 patients with advanced melanoma who had not received prior treatment for advanced disease in the phase III clinical trial. They were randomly assigned 1:1:1 to nivolumab plus ipilimumab, nivolumab, or ipilimumab.
Bristol-Myers immunotherapy combination extends survival in melanoma [Reuters] The new drugs do come at a hefty price. The combination regimen used in the study costs about $145,200, Bristol said.
	5.9.4 AACR - poumon
Five-Year Survival Observed With Opdivo (nivolumab) in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer (NSCLC), in Phase 1 Study CA209-003 [BMS] Estimated five-year overall survival rate in previously treated advanced NSCLC patients who received Opdivo was 16%; survival was observed across PD-L1 expression levels and tumor histologies.
Five-year Survival Rate For Nivolumab-treated Advanced Lung Cancer Patients Much Higher Than Historical Rate [AACR] This is the first report of the long-term survival rate in patients with metastatic NSCLC treated with an immune checkpoint inhibitor. Our study results show that for a small subset of patients, immunotherapy can work for a very long time.”
For Bristol-Myers, A Victory And A Mystery [Forbes] Given the positive results in skin cancer, and also in lung cancers that have not been helped by other treatments, why didn’t Bristol succeed in previously untreated lung cancer patients, the biggest market for these immune-boosting cancer drugs? Researchers have been scratching their heads asking that question.
	5.9.5 AACR - CAR-T
Kite Presents Ongoing Response Rate in Plenary Session from its Pivotal CAR-T Trial of Axicabtagene Ciloleucel in Patients with Aggressive Non-Hodgkin Lymphoma at the 2017 American Association of Cancer Research Annual Meeting [Kite] ZUMA-1 enrolled 111 patients of whom 101 were successfully treated with axicabtagene ciloleucel. ZUMA-1 patients were heavily pretreated and representative of those in the SCHOLAR-1 pooled analysis of refractory aggressive NHL.
Durability of CAR T-cell Therapy Response May Depend on Pretreatment Disease Burden in Leukemia Patients [AACR] A limitation of the study is that this is a retrospective analysis and the findings will need to be validated prospectively, Park said.
	5.9.6 AACR - prostate
Shorter Sleep Duration Is Associated With Increased Risk of Fatal Prostate Cancer in Younger Men [AACR] In all, the analysis included 407,649 men from CPS-I, followed from 1950 through 1972, and 416,040 men from CPS-II followed from 1982 through 2012. The study participants had self-reported numerous sleep-related behaviors, including sleep duration, shift work, and insomnia.
	5.9.7 AACR - divers
Regular Aspirin Use Is Associated with Lower Cancer Mortality [AACR] The researchers studied 86,206 women who were enrolled in the Nurses’ Health Study between 1980 and 2012, and 43,977 men who were enrolled in the Health Professionals Follow-Up Study from 1986 to 2012. They assessed aspirin use at baseline, then every two years after that.
Many Childhood Cancer Survivors Carry Mutations in Cancer Predisposition Genes, Raising Risk of Later Disease [AACR] Whole-genome sequencing conducted on a large cohort of childhood cancer survivors indicated that many survivors harbor mutations in cancer predisposition genes, significantly increasing their risk of developing a subsequent neoplasm (SN) later in life.
	5.9.8 AACR - Pharma
Seattle Genetics Presents Data Advancing Antibody-Drug Conjugate and Novel Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting [Seattle Genetics] Multiple presentations are being featured at AACR that highlight advances with Seattle Genetics’ ADC and empowered antibody pipeline programs.
#AACR17 roundup: Bristol-Myers, Merck KGaA and Pfizer in the spotlight, marking progress with checkpoints [EndPoints] Now that the first wave of PD-1 checkpoint inhibitors have been in use for awhile, we’re starting to see just how durable they can be for some patients.
	5.9.9 AACR - immunothérapies
Bristol-Myers Squibb Announces Results from CheckMate -143, a Phase 3 Study of Opdivo (nivolumab) in Patients with Glioblastoma Multiforme [BMS] CheckMate -143, a randomized Phase 3 clinical trial evaluating the efficacy and safety of Opdivo in patients with first recurrence of glioblastoma multiforme (GBM), did not meet its primary endpoint of improved overall survival over bevacizumab monotherapy.
Halozyme's PEGPH20 Increases Immune Response and Effectiveness of Immunotherapies in Preclinical Cancer Models [Halozyme] "We are pleased that PEGPH20 continues to demonstrate significantly improved tumor growth inhibition in certain hard-to-treat hyaluronan-rich cancer models when administered in combination with additional cancer fighting agents."
Biomarker May Identify Neuroblastoma Patients Most Likely to Benefit from Immunotherapy [AACR] According to Erbe, the main limitation of this study is that the number of patients in the two treatment groups was relatively small, and the subgroups with the different KIR/KIR-ligand genotypes were even smaller. Thus, the conclusions from this single study cannot be viewed as definitive and need to be validated, she explained.
Avelumab was Safe and Yielded Durable Responses for Patients With Advanced Merkel Cell Carcinoma [AACR] The researchers estimated that 74 percent of patients will have a response that lasts one year or longer.
AACR Annual Meeting 2017: Immunotherapy Provides Long-lasting Responses to Certain Cancer Types [Cancer Research Catalyst] For many patients whose cancers responded to treatment with an immune checkpoint inhibitor, particularly those that target the immune checkpoint proteins PD1 and PDL1, the responses appeared to have lasted for several years.
Avelumab Becomes First Approved Treatment for Patients with Merkel Cell Carcinoma [NCI] The new data, based on a median follow-up of 16.4 months, show a small increase in the overall response rate compared with 6 months of follow-up, from 31% to 33%. Ten patients had complete responses and 19 had partial responses, Howard L. Kaufman, M.D., of the Rutgers Cancer Institute of New Jersey, reported at the AACR annual meeting in Washington, DC.
	6.10.1 Politiques (USA)
Biden decries ‘draconian cuts’ to NIH in Trump’s proposed budget [STAT] Biden said the proposed $5.8 billion cut to the National Institutes of Health would be a stunning blow to scientific progress. “This would set the NIH budget, and biomedical research, back 15 years — and that’s not hyperbole,” Biden said.
Plan to Cut Funding for Biomedical Research Hits Opposition in Congress [NY Times] The president’s budget also proposes “a major reorganization” of the institutes to focus on “the highest-priority research and training activities.” The White House said Mr. Trump wanted “consolidations and structural changes” at the agency, which now has 27 institutes and centers, each with its own broadly defined mission.
	6.6 Publications
Journals retract paper, flag two others by cancer doc under investigation [Retraction Watch] Today, Croce received two expressions of concern (EOCs) from PNAS for two well-cited papers published over a decade ago, on which Croce — chair of the Department of Cancer Biology and Genetics at The Ohio State University (OSU) — is last author.