Onco Actu du 12 décembre 2019

	1. BIOLOGIE
Mechanism reprograms breast cancer to become metastatic [Baylor College of Medicine] Published this week in the Proceedings of the National Academy of Sciences, the study shows that hyperactive FOXA1 signaling, which previously was reported in endocrine-resistant metastatic breast cancer, triggers genome-wide reprogramming that results in enhanced resistance to treatment and metastatic behaviors.
Study Reveals Mechanisms That Help Pancreatic Cancer Cells Avert Starvation [NYU Langone] Published online December 11 in the journal Nature, the new work identifies the key molecular steps that are marshalled by the cancer cells to boost macropinocytosis.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
Three months later, the Trump administration's vaping policy is yet to be seen [CNN] Suspicion that the administration has backed down from plans to take flavored products off the market has led to sharp criticism from health advocacy groups and lawmakers.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Project GENIE Contributes Data on More Than 40,000 New Cancer Cases [Cancer Research Catalyst] The data released in the National Cancer Institute’s Genomic Data Commons (GDC) covers 294 unique cancer types, including many cases of rare bone and soft-tissue cancers new to the GDC. The contribution has more than doubled the number of cases in the GDC.
	5.10 TRAITEMENTS - ESSAIS
Novartis Kisqali® data show superior overall survival compared to fulvestrant and consistent efficacy across advanced breast cancer patient subgroups in MONALEESA-3 [Novartis] Kisqali is the only CDK4/6 inhibitor to demonstrate consistently superior overall survival in two Phase III trials, proven with multiple combination partners and in two distinct patient populations.
Lilly Opens First Ever Randomized Phase 3 Clinical Trial in Treatment-Naïve RET Fusion-Positive Non-Small Cell Lung Cancer [Lilly] Trial aims to enroll 400 patients with advanced or metastatic treatment-naïve RET fusion-positive NSCLC.
	5.12.13 IMMUNOTHÉRAPIES - BIOMARQUEURS
Look Beyond Molecular Testing to Predict Response to Immunotherapy Agents, Study Says [Dana-Farber Cancer Institute] The findings are based on data from the largest group of patients yet studied who had metastatic melanoma, were treated with drugs known as PD-1 inhibitors, had their tumor tissue analyzed for molecular abnormalities, and had the results linked to information on the course of their disease.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Novartis still hasn't solved its CAR-T manufacturing issues [Biopharma Dive] When it approved the cell therapy, the FDA identified non-viable cells as a "potential clinical safety issue." The new results suggest that may not be the case.
	5.4 TRAITEMENTS - ECONOMIE
Arguments on Drug Pricing [In The Pipeline] I am not asking everyone to immediately agree with Booth’s points or Scannell’s: but I am asking anyone who wants to seriously talk about these issues to take those arguments seriously. There are (to put it mildly) a lot of people who speak very loudly and confidently about drug research and drug prices who have no idea what they are talking about.
Targeted ovarian cancer drug made available to more people on NHS in England [Cancer Research UK] In this latest decision published at the end of November, NICE have extended olaparib’s use to those who have received 2 lines of chemotherapy, through the Cancer Drugs Fund (CDF) for patients who have had 2 lines of chemotherapy. The latest decision also confirmed it will continue to be routinely available to those who have had 3 or more lines of chemo.
Venturing A Perspective On The Drug Pricing Debate [Life Sci VC] As a front-line practitioner in early stage biotech venture capital, I can assure you that radical across-the-board cuts in the future pricing of innovative therapies will certainly affect both the scale and pace of investments in new biomedical startups.
	5.7.2 SABCS-DIVERS
SABCS: Pfizer's Ibrance backs up benefit in HER2-negative breast cancer with real-world data [Fierce Pharma] Pfizer said the data––culled from electronic records on the Flatiron Health Analytic database, which includes 2.2 million U.S. patients––supported results from its Paloma-2 clinical trial that showed a significant benefit in adding Ibrance to aromatase inhibitors.
	5.7.4 SABCS-ESSAIS
Combining Endocrine Therapy with a CDK4/6 Inhibitor Results In Similar Response Rates to Chemotherapy for High-Risk Luminal B Breast Cancer [SABCS] The study enrolled 106 patients, who were randomly assigned 1:1 to receive either the ribociclib and letrozole combination or multi-agent chemotherapy as neoadjuvant treatment. The intention-to-treat analysis included 101 patients who had tissue samples available at the time of surgery.
Addition of S-1 to Post-operative Endocrine Therapy Improves Outcomes for Patients with Hormone Receptor-positive, HER2-negative Breast Cancer [SABCS] Among the 957 patients in the S-1 arm, 101 experienced disease recurrence (iDFS events), compared to 155 of the 973 patients in the control arm (10.6 percent versus 15.9 percent).
New drugs show rare promise against advanced breast cancer [AP] One drug showed particular ability to reach tumors in the brain, which are notoriously tough to treat. The other pairs a sort of homing device for cancer cells with a payload of chemotherapy that’s released when it reaches its target.
	5.7.4.1 SABCS-ESSAIS-TUCATINIB
SABCS: Seattle Genetics hails 'stunning' tucatinib breast cancer data [Fierce Biotech] Approval would further validate Seattle Genetics' decision to buy Cascadian Therapeutics. Seattle Genetics paid more than $600 million to acquire Cascadian last year, in large part to get its hands on tucatinib.
Seattle Genetics Announces Positive Tucatinib HER2CLIMB Trial Results in Locally Advanced or Metastatic HER2-Positive Breast Cancer Presented at 2019 SABCS and Published in the New England Journal of Medicine [Seattle Genetics] First HER2 Tyrosine Kinase Inhibitor in Combination to Show Improved Progression-Free Survival and Overall Survival in Patients with Metastatic HER2-Positive Breast Cancer With or Without Brain Metastases.
Adding tucatinib to drug combination extends survival for advanced HER2+ breast cancer patients [MD Anderson Cancer Center] "Tucatinib in combination with trastuzumab and capecitabine should be the new standard of care for patients pretreated with multiple anti-HER2 agents including patients with brain metastasis.”
	5.7.4.2 SABCS-ESSAIS-TRASTUZUMAB DERUXTECAN
SABCS: AstraZeneca, Daiichi's ADC keeps breast cancer at bay for 16 months [Fierce Biotech] But the data weren't all rosy. Nearly all of the patients (99%) experienced side effects, including nausea, vomiting and low white blood cell counts. Fifteen percent of patients decided to stop treatment due to side effects, according to the statement. Twenty-five patients developed interstitial lung disease (ILD), which is characterized by scarring in the lungs. Most of them had mild cases, but four people died from the disease.
Targeted Drug Shows Promise Against HER2-Positive Breast Cancer That Stops Responding to Other Drugs [Memorial Sloan Kettering Cancer Center] “DS-8201a appears to work in people who have stopped responding to ado-trastuzumab emtansine,” Dr. Modi says. “One reason why is that DS-8201a has twice as many molecules of chemotherapy linked to each antibody. Additionally, the chemotherapy that’s attached has some unique properties that make it very effective.”
SABCS 2019 – Astrazeneca and Daiichi join the Her2 resistance [Vantage] New data confirms that trastuzumab deruxtecan has an exciting destiny, but the antibody-drug conjugate’s impressive efficacy in late-stage breast cancer comes at a price.
Trastuzumab deruxtecan achieved a tumour response rate of 60.9% in pivotal Phase II HER2-positive metastatic breast cancer trial [AstraZeneca] Patients achieved a disease control rate (DCR) of 97.3% with a median duration of response (DoR) of 14.8 months and median progression-free survival (PFS) of 16.4 months. The median overall survival (OS) has not yet been reached, with an estimated survival rate of 86% at one year.
AstraZeneca-Daiichi drug halts cancer for months in first readout [Reuters] The study dubbed DESTINY-Breast01 is the first of an envisaged 28 trials with trastuzumab deruxtecan.
What does $6.9B buy these days in oncology R&D? AstraZeneca has a landmark answer [EndPoints] All those data points explain why this drug got a breakthrough drug designation, followed by priority review with peak sales estimates falling at around $4.5 billion.
New HER2 Antibody-drug Conjugate Yielded Promising Clinical Responses in Breast Cancer Patients Pretreated with T-DM1 [SABCS] A limitation of the study is that this was a single-arm trial and therefore it is not possible to determine whether T-DXd is more effective than other therapies from these data.
	5.7.4.3 SABCS-ESSAIS-PERTUZUMAB
SABCS: Roche's Perjeta builds case as add-on to Herceptin with new analysis [Fierce Pharma] Perjeta showed the greatest clinical benefit in patients whose cancer had spread to the lymph nodes; 87.9% of that group was disease-free at the six-year mark, compared with 83.4% for the control arm.
APHINITY six-year results strengthen evidence of clinical benefit with Roche’s Perjeta-based regimen [Roche] Fewer deaths seen in Perjeta-based regimen arm, however overall survival data remain immature and statistical significance has not been reached at this interim analysis.
Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin comparable to intravenous formulations in people with HER2-positive breast cancer [Roche] Data will be submitted to health authorities globally, including the US Food and Drug Administration and European Medicines Agency.
Updated APHINITY Trial Data Show Addition of Pertuzumab to Trastuzumab Plus Chemotherapy Continues to Yield Clinical Benefit in Patients With Operable HER2-positive Early Breast Cancer [SABCS] Fewer deaths were seen in patients treated with pertuzumab, although the survival benefit was not statistically significant at this time.
	5.7.4.4 SABCS-ESSAIS-MARGETUXIMAB
MacroGenics Presents Results from the SOPHIA Study of Margetuximab in Patients with HER2-Positive Metastatic Breast Cancer at the San Antonio Breast Cancer Symposium [MacroGenics] Biologics License Application (BLA) submission to FDA expected before the end of 2019.
SABCS: MacroGenics' margetuximab posts OS gains in specific metastatic breast cancer patients [Fierce Biotech] The numbers again favored margetuximab, with a median OS of 21.6 months versus Herceptin’s 19.8, though with p-value of 0.326 the results were not statistically significant.
	5.8.3 ASH - DIVERS
At ASH, Researchers Discuss Rapid AML Nanopore Sequencing Assay for Analyzing Actionable Alterations [Genome Web] Although the test needs further validation and assessment in larger cohorts before it can be used in the clinical setting, the researchers are hoping that in the future, their assay may be a faster and more cost-effective alternative to the current gold standard approaches.
	5.8.6 ASH - LEUCÉMIES
Bristol-Myers shows off a low-profile AML contender it gained from Celgene buyout — and they’re taking it straight to the FDA [EndPoints] Celgene top-lined the positive results in a maintenance setting for acute myeloid leukemia a few months ago, but at ASH investigators pulled back the curtains on the all-important data they believe will give them an advantage in the commercial wars to come. And it’s impressive.
	6.6 PUBLICATIONS
Predatory journals: no definition, no defence [Nature] Leading scholars and publishers from ten countries have agreed a definition of predatory publishing that can protect scholarship. It took 12 hours of discussion, 18 questions and 3 rounds to reach.