Onco Actu du 2 janvier 2017

	1. Biologie
Radical new view of ovarian cancer implicates a ‘neglected’ origin [STAT] Research increasingly points to the likelihood that some of the most aggressive ovarian cancers originate in the fallopian tubes. Most doctors now believe there is little to lose by removing the tubes of women who are done bearing children — and potentially much to gain in terms of cancer prevention.
	3.1 Tabac
Chantix (varenicline) and Zyban (bupropion): Drug Safety Communication - Mental Health Side Effects Revised [FDA] The risk of these mental health side effects is still present, especially in those currently being treated for mental illnesses such as depression, anxiety disorders, or schizophrenia, or who have been treated for mental illnesses in the past. However, most people who had these side effects did not have serious consequences such as hospitalization.
FDA drops black box warning on Pfizer's anti-smoking drug [Reuters] Based on the data, an independent panel to the FDA in September narrowly voted in favor of removing the warning, arguing that the benefits of Chantix outweighed the demerits of its side-effects and that there was no clear evidence of causality between the drug and the side-effects.
	3.4.1 Chimioprévention - aspirine
Regular Aspirin Use May Reduce Risk for Pancreatic Cancer [AACR] Data from the new study and meta-analysis of data from 18 other studies suggest that over the past two decades, as the general population’s use of aspirin has increased, the effect of aspirin in decreasing pancreatic cancer risk has become more pronounced.
	3.7 Alcool
Breast cancer warning over wine was worded poorly, says health chief [The Guardian] Dame Sally Davies was accused of nanny state attitudes when she made the comments earlier this year to MPs at a science and technology select committee hearing.
	4.12 Biopsies liquides
Circulating tumour DNA technology: the future of cancer management? [PHG] Although promising, this technology is not a panacea for many of the challenges that affect the management of cancer, but now, and in the immediate future, it will have an important role to play in informing treatment decisions in non-small cell lung cancer, colorectal cancer and melanoma.
Searching for a blood test to monitor ovarian cancer [Cancer Research UK] While these early results are positive, the researchers do point out a few issues. First of all, the kind of trial they carried out is what’s known as retrospective. This means that they didn’t plan the samples they would collect ahead of time, rather they went back and looked at samples that were already available and analysed them.
Blood test which tells pancreatic cancer patients how long they have left to live, developed by scientists [The Telegraph] Scientists at the Sorbonne University in Paris discovered that the prognosis for patients is far worse if tumour DNA is found in their blood.
Tumor DNA in Blood May Serve as Prognostic Marker of Pancreatic Cancer [AACR] “Our study confirms, in one of the largest reported series, the feasibility of detecting ctDNA in patients with pancreatic adenocarcinoma using a specific next-generation sequencing (NGS) analysis method that allows us to screen a large number of genes,” said Jean-Baptiste Bachet.
	4.13 Dép., diag. & prono. - Peau
A Serum Biomarker May Predict Response to Immunotherapy Drugs That Target Immune Checkpoints [AACR] Serum levels of ANGPT2, a protein related to angiogenesis (blood vessel formation), was found to predict response to and influence the outcomes of treatment with a class of immunotherapeutics called immune checkpoint inhibitors in patients with advanced melanoma, according to a study published in Cancer Immunology Research.
	4.9 Dép., diag. & prono. - Sein
New Genetic Biomarker Identifies Patients With Increased Risk for Heart Damage Caused by Anthracycline Chemotherapy [AACR] “We found that the A allele of the single nucleotide polymorphism (SNP) rs28714259 was associated with increased risk of anthracycline-induced congestive heart failure among women with breast cancer.”
	5. Traitements
Some glioblastoma patients benefit from ‘ineffective’ treatment [Stanford Medicine] Glioblastoma patients with a high degree of vascularization of their tumors were found to have benefited from a treatment previously deemed ineffective, a new Stanford study shows.
Study potentially explains vulnerability of young cancer patients to treatment toxicities Reporting in Cancer Cell, they show that the tissues in these still-developing organs are more prone to apoptosis, or programmed cell death, when subjected to toxic stresses like chemotherapy and radiation.
New laser therapy for low-risk prostate cancer shows promise [NHS Choices] The results cannot be generalised to men with more advanced cancers – it's not known whether it would be safe and effective in other groups. The results also may not apply to all men defined as "low risk", only those defined as such when the study began in 2011.
Early-phase trial demonstrates shrinkage in pediatric neural tumors [NCI] In an early-phase clinical trial of a new oral drug, selumetinib, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage. NF1 affects 1 in 3,000 people.
Prostate cancer laser treatment could be a game changer for men [The Guardian] The idea of a drug made of harmless bacteria that can be activated by light to become cancer killers is not a new one. Photodynamic therapy is already being used to treat skin cancer and others where light can easily penetrate. Unfortunately, it has also been abused.
	5.10 Traitements - Essais
In Cancer Trials, a Lopsided Shot at Hope for Minorities [NY Times] Her effort was part of an unusual collaboration between the Queens center, where 92 percent of patients are from minority groups, and Memorial Sloan Kettering Cancer Center, one of the nation’s most renowned cancer hospitals.
	5.12 Immunothérapies
Vaccine ‘nanodiscs’ could personalize cancer immunotherapy [FierceBiotech] Each nanodisc contains patient-specific tumor neoantigens, which are genetic mutations in tumor cells, according to a press release. When given as a vaccine, the nanodiscs prompt the immune system to generate cancer-killing T cells that are preprogrammed to recognize the specific tumor in that patient’s body.
Cancer-Free: One Recovery Inspires Another — and Could Help Thousands [NY Times] In this story, the science reporter Denise Grady provides human backstory about her article about a woman who, remarkably, recovered from colon cancer after treatment with cells from her own immune system.
Innate Pharma woos Mondher Mahjoubi away from AstraZeneca’s cancer research ops to take the helm [EndPoints] Mahjoubi has been operating at AstraZeneca’s big MedImmune subsidiary in Gaithersburg, MD for the past three years, where it’s been hard at work on durvalumab, a PD-L1 checkpoint inhibitor likely destined to be the fourth or fifth such immuno-oncology program to hit the market.
Harnessing the U.S. Taxpayer to Fight Cancer and Make Profits [NY Times] Kite is one of a growing number of drug and biotech companies relying on federal laboratories. Analysts expect the company to charge at least $200,000 for the new treatment, which is intended as a one-time therapy for patients.
	5.12.1 Immunothérapies - partenariats
Medigene eyeing more immunotherapy deals after Bluebird pact [Reuters] The method is based on modifying T cells, one of the immune system's main weapons, to target specific tumor cells, but Medigene expects a market launch to be at least four and a half years away.
	5.12.2 Immunothérapies - CAR-T
Juno Therapeutics’ and Celgene Corporation’s Investigational Drug JCAR017 Granted Breakthrough Therapy Designation from FDA and Priority Medicines Eligibility from EMA for Relapsed/Refractory Diffuse Large B-cell Lymphoma [Juno] JCAR017 uses a defined CD4:CD8 cell composition and 4-1BB as the costimulatory domain, which differentiates it from other CD19-directed CAR T product candidates in clinical development.
CAR-T therapy makes early inroads in treating brain cancer [STAT] “This is the first example of CAR-T working in solid tumor cancers,” said Dr. Behnam Badie, chief of neurosurgery at City of Hope and a key investigator in the study.
Kite Pharma Announces Successful Defense of Roberts Patent and Intent to Appeal U.S. Patent and Trademark Office Decision on a Narrow Patent Focused on Select CD28 CAR-T Products [Kite] The USPTO's decision will have no impact on the timing of the rolling submission or review of the Biologics License Application for Kite's lead product candidate, axicabtagene ciloleucel (KTE-C19), a potentially lifesaving investigational therapy that has demonstrated the most advanced utilization of the CD28 costimulatory domain in a CAR-T therapy to date.
Juno Therapeutics Defeats Kite Pharma’s Challenge to CAR T-Cell Patent [Juno] The U.S. Patent & Trademark Office instituted a review of the patent and on December 16, 2016 issued a final written decision upholding all the claims of the patent.
	5.2 Pharma
Tesaro bags priority review, June PDUFA date for PARP inhibitor [FierceBiotech] Participants in the niraparib arm of the 553-person, double-blind, placebo-controlled study had an average progression-free survival (PFS) of 21 months, compared to 5.5 months for the control arm.
FDA Accepts Supplemental New Drug Application for Pfizer’s IBRANCE® (palbociclib) in HR+, HER2- Metastatic Breast Cancer [Pfizer] sNDA includes data from Phase 3 PALOMA-2 trial to support conversion from accelerated approval to regular approval.
Merrimack shutters a failing PhII breast cancer study for MM-302 [EndPoints] In the Phase II study, Merrimack recruited women who had already been treated with Herceptin, Perjeta and Kadcyla.
AstraZeneca oncology head jumps ship to become Innate CEO [Reuters] The loss of Mahjoubi is a setback for AstraZeneca, given the British drugmaker's focus on new cancer treatments. Mahjoubi previously worked at Roche's Genentech unit before joining AstraZeneca, where he has helped lead oncology strategy.
Seattle Genetics' cancer drug put on clinical hold after four deaths [Reuters] The drug, which has been granted orphan drug designation by both the U.S. FDA and the European Union for the treatment of AML, is also being tested in patients with myelodysplastic syndrome, another form of blood cancer.
	5.2.1 Pharma - Partenariats
Bristol-Myers doubles down on PsiOxus in $936M-plus “armed” oncolytic virus deal [EndPoints] Already allied on a combination of Opdivo with PsiOxus’ leading oncolytic virus, enadenotucirev, Bristol-Myers has come back for NG-348, an “armed” oncolytic virus that adds immuno-therapeutic transgenes to the cancer cell destroying mix.
In a first, AstraZeneca gains rights to an antisense KRAS drug in $165M Ionis deal [EndPoints] The drug targets KRAS, which spawns genetic mutations that figure prominently in cancer cases, giving AstraZeneca boasting rights to the first antisense drug with KRAS as a target that will enter clinical development.
	5.2.2 Pharma - Fusions & Acquisitions
Sumitomo Dainippon beefs up oncology pipeline with $780M Tolero buyout [EndPoints] Tolero has been at work building a case for its lead drug, the late-stage CDK9 inhibitor alvocidib, as a combination therapy suited to acute myeloid leukemia.
	5.2.3 Pharma - économie
Pharma's Pricing Troubles Will Get Worse in 2017 [Bloomberg] Though much of the anxiety has been over politically driven criticism and the potential for government price curbs, the only real pricing pressure in the U.S. has come from the private sector.
	5.3 Traitements - FDA, EMA, NICE...
E.U. Agency in Limbo as Hidden Costs of ‘Brexit’ Continue to Mount [NY Times] Most worrisome is an internal assessment suggesting that relocating the agency might mean losing up to half its personnel. That would be a big setback.
US drug approvals plummet in 2016 [Nature] Data highlight a slow year for the US Food and Drug Administration.
FDA: For Hospitals that Significantly Violated Federal Adverse Event Reporting Requirement, No Additional Action Necessary [The Cancer Letter] For some hospitals with significant violations of federal medical device reporting regulations, FDA officials said the agency received a response that was not adequate to address those violations.
FDA Finds Lapses in Reporting of Patient Harm, Deaths Resulting from Medical Devices in Hospitals Nationwide [The Cancer Letter] The agency’s report was published weeks before President Barack Obama signed the 21st Century Cures Act, a comprehensive health care reform and research funding measure that some critics lambasted for not including a medical device safety bill designed to address systemic lapses in reporting of adverse events.
	5.3.4 Traitements - AMM (FDA, EMA)
After an R&D odyssey filled with setbacks, Clovis wins an FDA OK for rucaparib [EndPoints] The FDA has approved its PARP inhibitor rucaparib, to be sold as Rubraca, to treat ovarian cancer cases with BRCA mutations. The drug is entering a market that will be sliced and diced by a variety of competitors.
Clovis Oncology Announces FDA Accelerated Approval of Rubraca™ (Rucaparib) for the Monotherapy Treatment of Advanced Ovarian Cancer in Women with Deleterious Germinale of Somatic BRCA Mutations Treated with Two of More Chemotherapies [Clovis] Rubraca received approval under the FDA’s accelerated approval program based on objective response rate and duration of response.
Another Notch For “PARP” Blockers As FDA Approves Clovis Cancer Drug [Xconomy] Even with this progress in ovarian cancer, the current reach of PARP blockers remains limited. But it’s possible that could change over the next few years. Pfizer, for instance, bought Medivation for $14 billion in part for an experimental PARP blocker, talazoparib, being tested in breast, lung, and prostate cancers. Tesaro’s niraparib is being tested in breast cancer, and AstraZeneca is exploring olaparib’s use in a variety of cancers as well.
FDA grants accelerated approval to new treatment for advanced ovarian cancer [FDA] The safety and efficacy of Rubraca were studied in two, single-arm clinical trials involving 106 participants with BRCA-mutated advanced ovarian cancer who had been treated with two or more chemotherapy regimens.
Clovis's ovarian cancer drug wins accelerated FDA approval [Reuters] The FDA also approved on Monday a test made by Foundation Medicine Inc to help detect the presence of BRCA mutations. If one or more mutations are detected, the patient is eligible for rubraca.
KEYTRUDA® (pembrolizumab) Approved as First Anti-PD-1 Therapy in Japan for First-Line Treatment of Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Express High Levels of PD-L1 [Merck] KEYTRUDA Also Approved for Second-Line Treatment of Patients with Advanced NSCLC Whose Tumors Express PD-L1.
European Medicines Agency’s CHMP Recommends Merck’s KEYTRUDA® (pembrolizumab) for the First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Have High PD-L1 Expression with No EGFR or ALK Positive Tumor Mutations [Merck] Opinion Based on Findings from KEYNOTE-024 Trial, Which Showed Superior Overall Survival and Progression Free Survival with KEYTRUDA Compared to Chemotherapy.
CHMP recommends EU conditional approval of Roche’s Alecensa (alectinib) for people with previously treated ALK-positive NSCLC [Roche] Alecensa as monotherapy is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib.
	5.4 Traitements - Economie
NICE says liver cancer treatment to stay within the Cancer Drugs Fund, but not recommended for routine NHS use. [NICE] The committee found that sorafenib does not provide enough benefit to patients to justify its high cost, even when special considerations were applied.
Kadcyla too expensive for routine funding on NHS [NICE] The drug, which costs around £90,000 per patient at its full list price, is licensed to treat HER2-positive breast cancer which has spread to other parts of the body, cannot be surgically removed and has stopped responding to initial treatment.
Germany’s Model For Drug Price Regulation Could Work In The US [Health Affairs Blog] Unlike single payer systems in Canada and the United Kingdom, Germany has a private multi-payer system where more than 90 percent of the insurance market is managed by non-profit “sickness funds.”
Japan to step up drug price reviews in bid to curb healthcare costs [Reuters] Last month, the government halved the price of cancer drug Opdivo, developed by Bristol Myers Squibb Co and Ono Pharmaceutical Co, on fears that a rapid uptake of the medicine would prove an intolerable burden on the healthcare system.
Breast cancer drug rejected for NHS use on cost-benefit grounds [The Guardian] “The reality is that the price of trastuzumab emtansine [the generic name for Kadcyla] is currently too high in relation to the benefits it gives for it to be recommended for routine commissioning in the NHS, even taking into account the end-of-life criteria and the patient access scheme.”
	6.1 Observation
The cancer registry is saving lives, but you’ve probably never heard of it [Cancer Research UK] From now on we’ll be working with other charities and national bodies like Public Health England to make sure that people understand more about the registry and how their data is used.
Cancer deaths will drop by 400,000 in next 20 years [Cancer Research UK] For every 100,000 people in the UK, 331 died from cancer in 2014. But by 2035 this number is predicted to drop to 280 per 100,000 people.
U.S. melanoma rates keep rising [Reuters] “The incidences of melanoma in situ (the earliest form of melanoma) and thin invasive tumors are increasing at a faster rate than that of thicker tumors, and the five-year survival rates are also improving, which is likely due to more melanomas being diagnosed at earlier stages.”
Many women get double mastectomy when only one breast has tumors [Reuters] In the subset of women without a genetic risk or identified mutation that boosts the odds for aggressive tumors, 12 percent still had both breasts surgically removed.
Older women with breast cancer still left out of medical trials [Reuters] In the trials of adjuvant treatments, the likelihood of enrollment by older women increased by 4 percent a year. But in the trials of neoadjuvant therapies and therapies for metastatic cancers, the likelihood that older women would participate actually decreased over time.
UK cancer death rates to fall by 15% by 2035 due to advances in research [The Guardian] However, although the risk of death from cancer is likely to fall, the number of people dying from it will continue to rise, because the ageing and growing population will result in more people being diagnosed, the charity said.
	6.10.1 Politiques (USA)
Biden to Create Moonshot Institute Independent of Cancer Centers [The Cancer Letter] The vice president appears to be finalizing plans for creating a foreign policy institute at the University of Pennsylvania and a domestic policy institute at the University of Delaware—both within driving distance of his home in The First State.
	6.5 Médecines alternatives
How cute. Naturopathic oncologists are pretending that theirs is a real medical specialty. [Respectful Insolence] That is one key reason why naturopathic oncology, like all of naturopathy, is a fake medical specialty and will remain so until it embraces science and evidence. Of course, that will never happen, because if naturopaths ever embraced science and evidence, their specialty would disappear.
	6.6 Publications
Cancer researcher in Germany loses multiple papers after misconduct finding [Retraction Watch] The notice for both papers cites an investigation involving Regine Schneider-Stock, who studies cancer biology at the Friedrich Alexander-University Erlangen-Nuremberg (FAU). Meanwhile, another 2005 paper that lists Schneider-Stock as the first author was retracted in October, noting evidence of image manipulation.
	6.8 Communication
News releases exaggerate the results of scientific research — a new study shows why this should stop [HealthNewsReview] For the study, researchers from the United Kingdom and Australia looked at 534 news releases issued by prominent journals, including the Lancet, BMJ, Nature and Science. The research team also analyzed the 534 journal articles associated with those releases, and 582 news stories that covered the research findings.
	6.9 Controverses
AA Gill’s death doesn’t mean the NHS is broken – or that private healthcare is superior [The Guardian] The journalist paid for a cancer drug not available for free, prompting outcry that NHS users are doomed. But there’s no system on Earth that’s foolproof.