Onco Actu du 7 décembre 2018

	3. Prévention
Risk-Reducing Mastectomy in BRCA1 and BRCA2 Mutation Carriers - A Complex Discussion [JAMA] As women contemplate their options, it is important to emphasize that these decisions need not be rushed. Indeed, close monitoring (including breast MRI) and support with open and recurrent dialogue may help women make choices that incorporate both their risks and preferences.
	4. Dépistage, diagnostic et pronostic
Dr. Lisa Schwartz, 55, Is Dead; Warned of Unnecessary Treatments [NY Times] Dr. Lisa Schwartz, who with her husband devoted her life to warning patients about the dangers of unnecessary medical tests and treatment and excessive diagnoses, died on Nov. 29 in Lebanon, N.H. She was 55. Her husband, Dr. Steven Woloshin, said the cause was cancer.
	4.10 Dép., diag. & prono. - FDA, EMA, NICE,...
Statement from FDA Commissioner Scott Gottlieb, M.D., on the FDA’s new effort for developing and class labeling of in vitro companion diagnostics for classes of oncology therapeutic products [FDA] The policy reflected in this guidance, when finalized, will make it easier for providers to use the same test in helping guide the use of a class of oncology therapeutic products, rather than one specific oncology therapeutic product within that class.
FDA Proposes New Steps to Advance Clinical Testing to Deliver New Cures [FDA] These developments are extremely promising. To fully realize these benefits, it’s critical that we continue to advance a modern framework for the development of advanced diagnostics — one that helps harness the full potential of new diagnostics to drive better treatment decisions with both current and future therapies, while also ensuring that such diagnostic tests are safe and effective.
	4.10 Dép., diag. & prono. - Poumon
Lung cancer screening part 2: research into detection technology could lead to better tests [Cancer Research UK] In part one of this series, we discussed clinical trials that have tested if CT scans could be used for lung screening. In part two, we investigate research that’s happening right now in the hunt for better ways to detect lung cancers early and give people a better chance of surviving.
	4.2 Dép., diag. & prono. - Génome
How DNA Companies Like Ancestry And 23andMe Are Using Your Genetic Data [Forbes] Since there is no real established precedent for DNA data, there are many issues that could come if your data is leaked and no laws to truly protect you at the moment.
The 100,000 Genomes Project has finished: what were the challenges and what comes next? [Institute of Cancer Research] The completion of 100,000 genomes marks the end of a chapter rather than the end of the story and earlier this year a new target was announced for the NHS to sequence one million genomes over the next 5 years.
	5. Traitements
The Promise—and Heartbreak—of Cancer Genomics [Wired] We live in a liminal age of cancer and precision medicine: Despite all the advances science has made, we still know very little and often can do less.
	5.1 Traitements - Pré-clinique
New hope for treating “chemo brain,” with a side of the joy of science [Stanford Medicine] In the new paper, published in Cell, Michelle Monje, MD, PhD, and her colleagues showed that microglia are conducting a symphony of problems in chemo brain. Chemotherapy over-activates the microglia, triggering malfunctions in two other types of glia.
How does chemo brain work? One cancer drug might interfere with brain signaling [Science] They found that depleting microglia was effective: It restored oligodendrocyte precursor cells, normalized myelin, and rescued short-term memory, the research team reports today in Cell. That means, they write, that the microglia are likely behind chemo brain for this particular drug.
	5.10 Traitements - Essais
Billions spent, but AbbVie can't catch a break with Rova-T as it cans SCLC trial [FierceBiotech] Rova-T (a.k.a Rovalpituzumab tesirine) targets the cancer stem cell-associated delta-like protein 3 (DLL3), which is expressed in more than 80% of tumors in SCLC patients.
AbbVie's Rova-T hits yet another setback [BiopharmaDive] Called TAHOE, the trial compared Rova-T to the chemotherapy topotecan in second-line advanced small cell lung cancer (SCLC). AbbVie said the decision to halt TAHOE does not affect other Rova-T studies. However, opportunities for the antibody-drug conjugate to prove effective are narrowing.
Worse Than Useless [In the Pipeline] If you’re an advocate for getting the FDA out of the way by whatever way you want to call it, because you’re convinced that it’s some sort of big slow roadblock to live-saving drugs reaching needy patients, I have something to say to you: Rova-T. It was new, it was promising, it was exciting, it was first-in-class, its toxicity was manageable, its early results were compelling, and a big drug company thought it was worth six billion dollars in cash up front. You would have given it to all those needy patients right then, back in 2016. Wouldn’t you? And killed them faster.
	5.12.2 Immunothérapies - CAR-T, thérapies cellulaires
NICE recommends a CAR T-cell therapy for adults with some types of non-Hodgkin lymphoma [NICE] Axicabtagene-ciloleucel is recommended within the Cancer Drugs Fund (CDF) giving people access to the treatment whilst more data is collected. CAR T-cell therapy for these lymphoma patients will be available at seven hospitals as the service is rolled out across the country.
	5.12.5 Immunothérapies - Pharma
Update on the Phase III EAGLE trial of Imfinzi and tremelimumab in advanced head and neck cancer [AstraZeneca] AstraZeneca will submit the results from the Phase III EAGLE trial for presentation at a forthcoming medical meeting.
AstraZeneca’s prized Imfinzi/tremelimumab combo fails again — this time in head and neck cancer [EndPoints] The late-stage EAGLE trial was testing Imfinzi monotherapy, as well as the combination of Imfinzi and tremelimumab, versus standard-of-care chemotherapy. Neither the monotherapy nor the combination met the main goals of improving overall survival, the company said, without offering further detail on the results, or providing any data on secondary endpoints such as progression-free survival.
AstraZeneca's Imfinzi fails to meet main goals in head and neck cancer study [Reuters] The results come after AstraZeneca warned last month that its immunotherapy treatment Imfinzi did not meet the main goal of improving survival rates for patients with the most advanced form of lung cancer, putting pressure on its shares.
	5.12.6 Immunothérapies - AMM
FDA approves Roche’s Tecentriq in combination with Avastin and chemotherapy for the initial treatment of people with a specific type of metastatic lung cancer [Roche] Approval based on survival benefit of Tecentriq in combination with Avastin, paclitaxel and carboplatin (chemotherapy) in people with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumour aberrations compared to Avastin plus chemotherapy.
Roche's lung cancer combo treatment wins FDA approval [Reuters] The long-awaited FDA decision is a shot in the arm to Roche’s aspirations of boosting Tecentriq sales in earlier lines of lung cancer treatment, but first-mover advantage of Merck’s Keytruda has dented the medicine’s prospects in one of cancer treatment’s most-lucrative segments.
	5.3 Traitements - FDA, EMA, NICE...
Statement from FDA Commissioner Scott Gottlieb, M.D., on FDA’s new strategic framework to advance use of real-world evidence to support development of drugs and biologics [FDA] This Framework is aimed at leveraging information gathered from patients and the medical community to inform and shape the FDA’s decisions across our drug and biologic development efforts. This strategic Framework will form a cornerstone of our efforts to advance the use of these tools.
	5.3.4 Traitements - AMM (FDA, EMA,...)
FDA Approves Three New Treatments for AML [Cancer Research Catalyst] Glasdegib is a molecularly targeted therapeutic directed against a protein called Smoothened. Venetoclax is a molecularly targeted therapeutic directed against the protein BCL-2. Gilteritinib is the third molecularly targeted therapeutic approved recently by the FDA for the treatment of AML. It targets the protein FLT3 and it is intended for use in the treatment of adults of any age whose leukemia tests positive for a mutation in the FLT3 gene, and that has relapsed after initial treatment or did not respond to initial treatment.
	5.7.1 SABCS-communiqués
Puma Biotechnology Presents Results of Patient Reported Outcomes in Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the 2018 San Antonio Breast Cancer Symposium [Puma] The presentation entitled, “The impact of neratinib with or without anti-diarrheal prophylaxis on health-related quality of life in HER2-positive early stage breast cancer: Analyses from the ExteNET and CONTROL trials.” is being presented by Dr. Suzette Delaloge, Institut Gustave Roussy, Paris, France.
Puma Biotechnology Presents Results from the Hormone Receptor Positive Subgroup in Phase III ExteNET Trial of Neratinib for HER2-Amplified, Early Stage Breast Cancer at the 2018 San Antonio Breast Cancer Symposium [Puma] ExteNET was a Phase III multicenter, randomized, double-blind, placebo-controlled trial of neratinib in adult patients (n=2,840) with early stage HER2-positive breast cancer following adjuvant trastuzumab treatment. Participants were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year.
Puma Biotechnology Presents Results from the Phase II SUMMIT Trial of Neratinib for ERBB2 (HER2) Mutant, HER2 Non-Amplified, Metastatic Breast Cancer at the 2018 San Antonio Breast Cancer Symposium [Puma] The Phase II SUMMIT basket trial is an open-label, multicenter, multinational study to evaluate the safety and efficacy of neratinib administered daily to patients who have solid tumors with activating HER2 or HER3 mutations.
Myriad Validates Polygenic Score to Predict Breast Cancer Risk in Women of Hispanic Ancestry Who Test Negative for Hereditary Cancer Mutations [Myriad] The clinical implementation of riskScore for women of Hispanic ancestry may significantly improve the management of high-risk Hispanic women who test negative for mutations in with the myRisk Hereditary Cancer test.
	5.7.2 SABCS-divers
Liquid Biopsies in SOLAR-1 Trial Predict Benefit of Alpelisib in PIK3CA-Mutant Breast Cancer [AACR] In addition to tissue-based analysis, the researchers evaluated progression-free survival (PFS) by PIK3CA mutational status as measured in circulating tumor DNA (ctDNA). PFS was also analyzed by line of metastatic treatment, and by prior exposure to cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.
Novartis investigational BYL719 (alpelisib) plus fulvestrant consistently improved PFS in patients with PIK3CA mutated HR+/HER2- advanced breast cancer in new SOLAR-1 analyses [Novartis] SOLAR-1 is the first Phase III breast cancer trial to demonstrate potential viability of using liquid biopsy to select patients for targeted treatment.
	5.7.3 SABCS-AACR
Black Women Have Worse Breast Cancer Outcomes Despite Receiving Similar Treatment as White Women [AACR] Albain and colleagues analyzed the association between clinical outcomes and race in participants from the TAILORx trial, which evaluated more than 10,000 women with the most common type of early breast cancer (hormone receptor-positive, HER2-negative, axillary lymph node-negative).
Accelerated Partial Breast Irradiation, Although Close, was Not Equivalent to Whole Breast Irradiation To Control Ipsilateral Breast Tumor Recurrence [AACR] “Despite only small differences in IBTR (<1 percent) and RFI (1.5 percent) between the two treatment arms at 10 years, we could not declare that WBI and PBI were equivalent in controlling local in-breast tumor recurrence because the hazard ratio between arms fell short of meeting statistical equivalence.”
Axillary Radiotherapy and Lymph Node Surgery Yielded Comparable 10-year Outcomes for Patients with Breast Cancer [AACR] “Given that we previously published five-year follow-up data from the trial showing that lymphedema occurred significantly more often after axillary lymph node dissection than after axillary radiotherapy, we believe that axillary radiotherapy should be considered a good option for patients who have a positive sentinel lymph node biopsy instead of complete surgical clearance of the axillary lymph nodes.”
Circulating Tumor Cell Count Could Help Choose Treatment for Metastatic Breast Cancer Patients [AACR] In this trial, 778 patients were randomly assigned 1:1 to a clinically driven treatment arm (hormone therapy or chemotherapy was administered as decided by a physician based on clinical factors) or a CTC-driven treatment arm (hormone therapy was administered if 7.5 ml blood had less than 5 CTC and chemotherapy was administered if 7.5 ml blood had 5 or more CTC).
Low-Dose Tamoxifen Was Safe and Effective at Reducing Recurrence and New Breast Disease for Patients With DCIS, LCIS, and ADH [AACR] De Censi and colleagues randomized 500 women with DCIS, LCIS, and ADH who had been treated with surgery and, if needed, radiotherapy to either low-dose tamoxifen or placebo. Treatment continued for three years and patients were seen by the research team every six months and had a mammogram annually.
	5.7.4 SABCS-essais
Major EORTC trial presented at San Antonio Breast Cancer Conference: 10-year follow-up of AMAROS shows benefits for post-operative radiotherapy to the axilla in patients with a tumour-positive sentinel node [EORTC] Before their sentinel nodes were biopsied for the presence of tumour cells, they were randomised into the two groups. Cancer was found in the sentinel nodes of 1425 patients and were randomized: 744 had complete axillary surgery and 681 had radiotherapy to the axillary lymph nodes. The ten-year analysis in 1425 sentinel node positive patients showed that there was a very low incidence of cancer recurrence in the breast and the armpit in both groups.
	6.12 Ethique
Top cancer center’s business deals created a web of conflicts, say ethics experts [STAT] STAT’s examination comes as Memorial Sloan Kettering faces criticism for other business arrangements.
	6.5 Médecines alternatives/complémentaires
The case of Omer Ahmetovic: Naturopathy, cancer, tragedy, and homicide [Respectful Insolence] Last year, Fikreta Ibrisevic chose a naturopathic quack named Juan Gonzalez to treat her cancer. She had been planning on conventional therapy, but Gonzalez convinced her that "chemo is for losers" and that he could cure her without the toxicity of surgery, chemotherapy, and radiation. As a result, she died. Her distraught husband Omer Ahmetovic killed the quack.
	6.6 Publications
ORCID Open Letter - Funders [ORCID] We, the following funding bodies, commit to implementing ORCID iDs in accordance with their best practice guidelines for funders. We encourage other funders to join us in this initiative.
	6.7 DMP, Big Data & applis
What specific protections apply to health-related, genetic, or biometric data? [Global Alliance for Genomics and Health] In the eyes of the GDPR, not all data are equal. Rather, ‘special categories’ of personal data are given additional protection. For our purposes, there are three special categories of note.
	6.7.1 IA/bioinformatique
Artificial intelligence in pharma, health care: at the crossroads of hype and reality [STAT] While we are not recommending that the U.S. regulatory framework be dismantled, it is becoming increasingly apparent to us how much technological innovation in U.S. health care is held back by an acute “anti-change culture” on the part of clinicians, management, and funding sources.