Onco Actu du 2 septembre 2019

	2.8 ETIOLOGIE - CONTRACEPTIFS, THS
Hormone therapy during menopause raises breast cancer risk for years, study finds [STAT] The new analysis doesn’t show that MHT directly causes breast cancer. But researchers suspect the association has to do with the hormonal changes of menopause.
Breast cancer risk from using HRT is ‘twice what was thought’ [The Guardian] The research, published in the Lancet medical journal, says one in 50 women of average weight taking the most common form – combined daily oestrogen and progestogen – for five years will get breast cancer as a result.
	3.1 PRÉVENTION - TABAC
Anti-smoking advocates bemoan “faltering” pace of FDA action [AP] Efforts to bolster cigarette warnings and ban harmful ingredients have been stymied by tobacco companies. And the pace of progress is so slow that the FDA now faces lawsuits from its traditional allies: anti-smoking groups who are suing the agency to take action.
The F.D.A.’s New Cigarette Warnings Are Disturbing. See for Yourself. [NY Times] Nine years after the Food and Drug Administration first proposed graphic images as warnings on cigarette packs but was thwarted by tobacco companies in a successful court battle, the agency announced on Thursday that it is finally issuing a new set.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
The Mysterious Vaping Illness That’s ‘Becoming an Epidemic’ [NY Times] Dr. Scott Gottlieb, the former commissioner of the Food and Drug Administration, said he suspected a link to illicit products — perhaps related to ingredients including THC — because the main manufacturers of e-cigarettes had not suddenly altered their ingredients on a wide scale.
Exclusive: India proposes ban on e-cigarettes, with jail terms for offenders - government documents [Reuters] The ministry has proposed that the government issue an executive order banning the devices in the public interest, saying it was needed to ensure e-cigarettes don’t become an “epidemic” among children and young adults.
FTC probes marketing practices of e-cigarette maker Juul: source [Reuters] FTC investigators are examining Juul’s involvement in deceptive marketing, including by targeting minors or using influencers, and is also determining whether to seek monetary damages, according to the Wall Street Journal report.
CDC probes lung illnesses linked to e-cigarette use [Reuters] The CDC is working with health departments in Wisconsin, Illinois, California, Indiana and Minnesota on the investigation. Since June 28, states have reported 94 possible cases of severe lung illness tied to vaping, primarily among teenagers and young adults, according to a CDC statement on Saturday.
E-cigarette firms probed over health concerns by U.S. House panel [Reuters] The letter to Juul asked if the company has conducted or financed studies on the health implications of using its products and the effectiveness of Juul in helping users quit smoking.
	4. DÉPISTAGE, DIAGNOSTIC ET PRONOSTIC
Lack of government action on NHS staffing undermines ambition to diagnose cancer early [Cancer Research UK] “NHS staff are working as hard as they can, but we won’t be able to care for the rising number of cancer patients unless the resources are found to train more specialist staff. Extra scanners are welcome, but they will achieve nothing without staff to run them and experts to interpret the scans. It’s like buying a fleet of planes with no pilots to fly them.”
	4.15 DÉP., DIAG. & PRONO. - IMAGERIE
Prostate-imaging camera captures molecular detail to detect cancer [Stanford Medicine] Gambhir's new technology, dubbed the transrectal ultrasound and photoacoustic device, or TRUSPA, marries ultrasound and photoacoustic imaging techniques to simultaneously produce a picture showing the anatomy of the prostate, functional details about the gland and molecular information that can help flag cancerous tissue.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
U.S. Preventive Services Task Force Issues Final Recommendation Statement on BRCA-Related Cancer Prevention [USPSTF] Some women may benefit from risk assessment, counseling, and testing for rare genetic mutation.
New Guidelines Expand BRCA Screening [The Scientist] US Preventive Services Task Force recommends genetic testing for mutations in the cancer-related genes for more—but not all—women.
	5. TRAITEMENTS
Roche's effort to stop cancer metastasis unexpectedly leads to a Merck drug [Fierce Biotech] With the new information on CCR7’s structure, the researchers were able to screen for drugs that block its signaling. During that process, they found a match in a drug that Merck & Co. is already testing in people, navarixin (MK-7123). They published the discovery in the journal Cell.
	5.10 TRAITEMENTS - ESSAIS
Many clinical trials for new cancer drugs didn’t include any data on race [STAT] Taken together, Raghav said the findings raise questions about what the disparities might suggest about how researchers recruit for and run clinical trials.
A Double Whammy of Non-Good News About Non-Inferiority Trials [Absolutely Maybe] With the pace and influence of these trials heating up, I hope there’s a good review coming down the line to get this into perspective. If the number and influence of these trials keeps growing without them being rigorous enough, this is a critical issue.
FDA finalizes guidance on placebos and blinding for cancer trials [EndPoints] According to guidance, placebos should only be considered in randomized controlled trials to treat oncologic disease or hematologic malignancy “when surveillance is standard of care” or in studies with “certain trial design features (e.g., when the trial uses an add-on design).”
	5.12.1 IMMUNOTHÉRAPIES - PARTENARIATS
Celgene pays Immatics $75M to work on solid tumor cell therapies [Fierce Biotech] Immatics has the technology to develop multiple types of adoptive cell therapies, from selected and expanded pools of a patient’s own T cells through to off-the-shelf therapies engineered to recognize cancer cell targets. The German biotech has other technologies for finding oncology targets and T-cell receptors (TCRs).
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Adaptimmune pens backloaded deal to access T-cell tech [Fierce Biotech] Noile-Immune is a Japanese chimeric antigen receptor T-cell (CAR-T) player built on technology developed by Yamaguchi University’s Koji Tamada. In mice, CAR-T cells engineered using the technology to express IL-7 and CCL19 performed better than conventional CAR-T therapies and were associated with increased infiltration of dendritic cells and T cells into tumors.
	5.12.3 IMMUNOTHÉRAPIES-COMBINAISONS
AstraZeneca's Imfinzi-tremelimumab duo flops another late-stage lung cancer trial [Fierce Pharma] Researchers did the primary analysis among patients with high levels of mutations in their tumors, an experimental biomarker called tumor mutational burden (TMB). Companies including AZ and Bristol-Myers Squibb have said the marker could help identify patients who respond best to their therapies, but so far, trials haven’t shown that to be the case—including this one.
AstraZeneca lung cancer miss is Merck's gain [Biopharma Dive] While Imfinzi is now a standard treatment in the adjuvant setting, negative results from NEPTUNE and an earlier trial called MYSTIC limit the drug's expansion.
Update on the Phase III NEPTUNE trial of Imfinzi plus tremelimumab in Stage IV non-small cell lung cancer [AstraZeneca] In the primary analysis population of patients whose blood TMB was 20 or more mutations per megabase (mut/Mb), the combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving OS compared to SoC chemotherapy.
AstraZeneca’s Imfinzi/treme combo strikes out — again — in lung cancer. Is it time for last rites? [EndPoints] We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.
AstraZeneca Imfinzi combination fails advanced lung cancer study [Reuters] The late-stage clinical trial was testing Imfinzi, chemically known as durvalumab, along with another treatment tremelimumab and compared the combination to platinum-based chemotherapy to treat patients whose cancer had spread beyond the lungs.
	5.12.6 IMMUNOTHÉRAPIES - AMM
Roche's Tecentriq grabs I-O's first European OK for triple-negative breast cancer [Fierce Pharma] Regulators based the decision on data from the phase 3 Impassion130 trial, which showed that adding Tecentriq to Abraxane in new patients could slash the risk of disease worsening or death by 20%. The combo kept cancer at bay for a median 7.2 months, compared with 5.5. months for solo Abraxane.
EMA follows FDA to approve Roche's Tecentriq combo for frontline use in triple negative breast cancer [EndPoints] The approval, which covers patients whose tumors express PD-L1, is key for the Swiss drugmaker that is third-in-line — behind Merck and Bristol-Myers Squibb — for the checkpoint inhibitor Iron throne.
Roche immunotherapy Tecentriq gains European approval for breast cancer [Reuters] Tecentriq, having steadily added approvals in new cancer indications and new geographies, is on track to surpass $1.5 billion in annual sales in 2019, its third full year on the market.
European Commission approves Roche’s Tecentriq in combination with Abraxane for people with PD-L1-positive, metastatic triple-negative breast cancer [Roche] The Tecentriq combination marks the first cancer immunotherapy regimen to be available in Europe for triple-negative breast cancer – an aggressive and difficult-to-treat disease.
	5.13 WCLC
Merck Highlights New Data from Leading Lung Cancer Clinical Development Program at the IASLC 2019 World Conference on Lung Cancer [Merck] Pooled Overall Survival (OS) Data from Three Trials with KEYTRUDA® (pembrolizumab) Plus Chemotherapy in Subgroup of Patients with Non-Small Cell Lung Cancer (NSCLC) Whose Tumors Do Not Express PD-L1.
	5.17 TRAITEMENTS - RADIOTHÉRAPIE
Why a Promising, Potent Cancer Therapy Isn't Used in the US [Wired] Carbon ion radiation therapy is being used to blast tumors all over the world. Just not in the country that invented it.
	5.2.1 PHARMA - PARTENARIATS
Presage inks its 3rd deal around phase 0 studies—with more to come [Fierce Biotech] Presage’s CIVO platform is designed to deliver up to eight different microdoses of drugs or drug combinations directly into the tumor. Each drug or combination is injected alongside fluorescent tracking microspheres, which allow investigators to track each dose.
Bristol-Myers opens up the Phase 0 pathway in testing its new cancer therapies, following in Celgene’s footsteps [EndPoints] So it’s particularly interesting to see Bristol-Myers tie-up with Seattle-based Presage Biosciences on Phase O testing, which will use microdoses of multiple drugs and combos on patients to gauge their pharmacodynamic effects.
	5.2.2 PHARMA - FUSIONS & ACQUISITIONS
When it comes to cancer drug deals, one hot protein family is raking in billions: report [Fierce Pharma] So which kinase is the hottest target right now? That would be Bruton’s tyrosine kinase (BTK), which has been implicated in several cancers, including chronic lymphocytic leukemia and mantle cell lymphoma. BTK inhibitors have driven four deals worth a total of $27 billion since 2010, according to SVB Leerink.
	5.2.4 PHARMA - ABBVIE
It's official—AbbVie dumps Rova-T after another lung cancer fail [Fierce Biotech] Rova-T’s promise lay in targeting delta-like protein 3 (DLL3), which is expressed in more than 80% of tumors in patients with small-cell lung cancer (SCLC).
AbbVie ends Rova-T research after another study setback [Biopharma Dive] A string of clinical failures derailed AbbVie's ambitions for the cancer drug, which was once predicted to earn billions of dollars in peak sales.
AbbVie abandons late-stage lung cancer asset Rova-T [Reuters] The drugmaker acquired Rova-T through its $5.8 billion acquisition of Stemcentrx in 2016, but recorded impairment charges of about $4 billion in January after it halted enrolment of a separate study testing the therapy.
AbbVie Discontinues Rovalpituzumab Tesirine (Rova-T) Research and Development Program [AbbVie] MERU, a Phase 3 placebo-controlled trial evaluating Rova-T as a first-line maintenance therapy for advanced small-cell lung cancer (SCLC), demonstrated no survival benefit for patients receiving Rova-T at the interim analysis.
	5.2.5 PHARMA - GSK
Moving quickly, GSK to advance myeloma drug on new data [Biopharma Dive] In its Phase 2 study, GSK tested belantamab mafodotin in 196 patients previously treated with at least three other drugs and are refractory to two of the main treatment classes now available.
GSK's Hal Barron heralds their second positive pivotal for crucial anti-BCMA therapy, pointing to a push for quick OKs in a crowded field [EndPoints] The drug also represents a comeback of sorts for antibody-drug conjugates, where enthusiasm had flagged. The therapy uses an anti-B cell maturation antigen (BCMA) monoclonal antibody “conjugated” to the cytotoxic agent auristatin F via a non-cleavable linker, supplied by Seattle Genetics.
GSK announces positive headline results from the pivotal DREAMM-2 study for multiple myeloma [GSK] Belantamab mafodotin (GSK2857916) on track for regulatory submission by the end of 2019.
GSK builds oncology pipeline as drug shown to help myeloma patients [Reuters] The interim result gives further credence to a class of molecules known as antibody drug conjugates (ADC) that belantamab mafodotin belongs to.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
EMA and FDA historically agree on just about every new drug approval, but is that slowly changing? [EndPoints] The study also notes how the FDA more commonly granted accelerated approvals (12/25 in oncology and 5/8 in hematology) than the EMA granted conditional marketing authorization or authorization under exceptional circumstances (7/25 in oncology and 2/8 in hematology).
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
Janssen Announces European Commission Approval of Imbruvica®▼(ibrutinib) for Expanded Use in Two Indications [Janssen] This includes the use of ibrutinib in combination with obinutuzumab in adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and the use of ibrutinib plus rituximab for the treatment of adult patients with Waldenström's macroglobulinemia (WM).
European Commission Approves Empliciti (elotuzumab) Plus Pomalidomide and Low-Dose Dexamethasone (EPd) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma [BMS] Second Empliciti-based combination approved in Europe for patients with relapsed and refractory multiple myeloma.
Bristol-Myers, AbbVie's multiple myeloma drug wins second EU nod as part of triple regimen [EndPoints] The approval is based on data from the 117 patient-ELOQUENT-3 trial in which the triplet doubled both median progression-free survival (PFS) and overall response rate (ORR) among patients with relapsed and refractory multiple myeloma, versus pomalidomide and low-dose dexamethasone alone.
FDA approves third oncology drug that targets a key genetic driver of cancer, rather than a specific type of tumor [FDA] This is the third time the agency has approved a cancer treatment based on a common biomarker across different types of tumors rather than the location in the body where the tumor originated.
Roche's personalized cancer treatment wins FDA approval [Reuters] Since these NTRK fusions occur in a multitude of tumors, Roche sees potentially broad application for Rozlytrek, in conjunction with diagnostic tests from its Foundation Medicine unit.
FDA approves Celgene's bone marrow cancer treatment [Reuters] Inrebic belongs to a class of drugs known as JAK inhibitors that work by blocking inflammation-causing Janus kinases enzymes. It will compete with Incyte Corp’s Jakafi, also a JAK inhibitor, which was approved in 2011 for treating the same condition.
Roche cancer treatment priced at $17,050 a month, lower than rival Vitrakvi [Reuters] Vitrakvi, co-developed by Bayer and Lilly’s Loxo Oncology, won approval in November, and is priced at $32,800 per month.
	5.4 TRAITEMENTS - ECONOMIE
Olaparib for maintenance treatment of BRCA mutation-positive advanced ovarian, fallopian tube or peritoneal cancer after response to first-line platinum-based chemotherapy [NICE] Olaparib (Lynparza) is available through the Cancer Drugs Fund. It is a possible treatment for advanced ovarian, fallopian tube or peritoneal cancer in adults, if they have a BRCA mutation and the cancer has been treated with 1 course of platinum-based chemotherapy.
	6. LUTTE CONTRE LES CANCERS
For a decade, Francis Collins has shielded NIH—while making waves of his own [Science] After 10 years, Collins has plenty on his to-do list. He wants to expand NIH's support of artificial intelligence and machine learning and is looking to hire a data czar, probably from Silicon Valley. He's also excited about gene therapy, which is finally reaching the clinic for some inherited childhood diseases.
	6.1 OBSERVATION
Childhood cancer survivors face variety of heart risks [Reuters] The researchers focused on the 7,289 cancer survivors who had been diagnosed before age 18, treated at a pediatric cancer center between 1987 and 2010, and survived at least 5 years.
As Americans get heavier, obesity-linked cancers may strike earlier [Reuters] In their analysis of more than six million cancer cases, researchers found that obesity-associated cancers appeared to be shifting to younger people, including those under 50, according to the report published in JAMA Network Open.
	6.10 POLITIQUES
The Government has announced it will establish a new Cancer Control Agency by the end of the year [Science Media Center] Recently New Zealand has been falling behind in its performance for cancer treatment compared to a number of other countries. And the disparities in cancer outcomes for Māori and Pacific peoples leaves us ashamed of our failure to make any headway there. So what will be different with the new plan?
	6.11 PATIENTS
The Emperor of All Maladies’ New Clothes [NY Times] A physical and psychological trial, cancer also poses the ongoing challenge of finding apparel for bodies altered by treatment.
	6.6 PUBLICATIONS
More than 700 German research institutions strike open-access deal with Springer Nature [Science] Agreement will make thousands of German-authored papers available free worldwide every year.
In departure for NIH, Cancer Moonshot requires grantees to make papers immediately free [Science] That is a big change from the current policy at the National Institutes of Health, NCI’s parent agency. NIH requires only that final papers be available through NIH’s full-text PubMedCentral site within 12 months of publication—a delay that publishers cherish, saying that it safeguards subscription revenues and keeps journals viable.
	6.7.1 IA/BIOINFORMATIQUE
The “inconvenient truth” about AI in healthcare [Digital Medicine] However, “the inconvenient truth” is that at present the algorithms that feature prominently in research literature are in fact not, for the most part, executable at the frontlines of clinical practice.
	6.9 CONTROVERSES
Scientists Avoid Bias When They Know They're Being Tested [Wired] It's possible to set up artificial test situations that are better controlled, but people's behavior changes when they know they're being tested. That is precisely the message that's driven home by a new paper that looks at gender bias in the awarding of research positions in France.