Onco Actu du 13 décembre 2019

	1. BIOLOGIE
Metabolic adaptation ensures survival of colon cancer cells [DKFZ] Colon cancer cells deficient in p53, one of the most important control proteins in cell growth, activate a particular metabolic pathway to adapt to the lack of oxygen and nutrients inside the tumor. Statins, which are often prescribed to lower cholesterol, block this metabolic pathway and cause the cancer cells to die, as scientists from the German Cancer Research Center (DKFZ) have now discovered.
	2.8 ETIOLOGIE - CONTRACEPTIFS, THS
More women should take hormone-replacement therapy [The Economist] It’s safer than people think and has large health benefits for many.
	3.1.1 PRÉVENTION - TABAC - E-CIGS
The Height of Irresponsibility: Massachusetts Department of Public Health Tells Public the Cause of Respiratory Disease Outbreak is Unknown [The Rest of the Story] By conflating the respiratory disease outbreak with the general problem of youth vaping, the Department has successfully fooled both the public and policy makers into believing that e-cigarettes are causing youth to suffer severe respiratory failure.
Anti-Vape Laws Could Do More Harm Than Good [Wired] Banning vaping just might drive teens to the black market—and send adult smokers back to their cancer sticks.
	4.15 DÉP., DIAG. & PRONO. - IMAGERIE
New algorithm detects even the smallest cancer metastases across the entire mouse body [MedicalXPress] The DeepMACT algorithm matched the performance of human experts in detecting the metastases—but did so more than 300 times faster. The study is published in Cell.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Universal Genetic Testing in Breast Cancer May Result in More Harm Than Good, Experts Worry [Genome Web] The ACMG's position is notably in contrast to the ASBrS, and others in the field who would like to see less restrictive testing guidelines in the era of multi-gene panels.
Breast cancer patients to be evaluated for genetic testing [EurekAlert!] According to a statement on behalf of the American College of Medical Genetics and Genomics (ACMG) published Dec. 13 in the organization's official journal, Genetics in Medicine, there is insufficient evidence to recommend universal genetic testing for BRCA1/2 alone or in combination with multi-gene panels for all breast cancer patients.
	5.1 TRAITEMENTS - PRÉ-CLINIQUE
Ultrasound blasts potent glioblastoma drug into brain tumor [EurekAlert!] Treatment successfully delivers drug across the blood-brain barrier directly to brain tumor in mice.
	5.10 TRAITEMENTS - ESSAIS
Osimertinib Improves Survival in Advanced Lung Cancer with EGFR Mutations [NCI] In the trial, dubbed FLAURA, patients with advanced NSCLC who received osimertinib as an initial treatment lived approximately 7 months longer than patients treated with erlotinib (Tarceva) or gefinitib (Iressa).
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
Gilead's Kite files for FDA approval of second CAR-T therapy [Fierce Biotech] The data suggest KTE-X19 can find a role in the mantle cell lymphoma (MCL) treatment pathway. Use of BTK inhibitors such as Imbruvica has improved response rates in MCL patients in recent years, but the prognosis for people who progress after treatment with these drugs is poor.
Kite Pharma, Juno duke it out in court over megamillion-dollar CAR-T patent [Fierce Pharma] Juno Therapeutics, now part of Bristol-Myers Squibb, is hoping to prove that Gilead’s Kite Pharma unit is infringing a patent with its blood cancer therapy Yescarta. And the two sides got their chance to air their arguments in court this week.
On the heels of promising MCL data, Kite hustles its 2nd CAR-T to the FDA as the next big race in the field draws to the finish line [EndPoints] That’s the data that Kite will now take to the FDA, which is likely to respond with alacrity to a new application with good odds of delivering the third CAR-T in the field.
Kite Pharma's ex-CEO contradicts founder as CAR-T patent trial heats up, with conflicting valuations [EndPoints] Kite Pharma, a Gilead subsidiary now, is being sued by Sloan Kettering and Juno Therapeutics, the company to whom Sloan Kettering licensed their CAR-T treatment, for patent infringement.
	5.12.6 IMMUNOTHÉRAPIES - AMM
AstraZeneca rounds out stellar China year—and beats Roche to the punch—with Imfinzi lung cancer nod [Fierce Pharma] Chinese regulators doled out the new go-ahead based on strong data from the phase 3 Pacific trial, which has helped make Imfinzi the new standard of care in that particular indication and a blockbuster drug with sales collected from more than 50 countries around the world.
Imfinzi approved in China for the treatment of unresectable, Stage III non-small cell lung cancer based on the Phase III PACIFIC trial [AstraZeneca] Imfinzi (durvalumab) is the only immunotherapy approved in China to treat patients in the curative-intent Stage III setting following chemoradiation treatment.
AstraZeneca joins Merck, Bristol-Myers in China's checkpoint race as regulators OK first PD-L1 [EndPoints] For AstraZeneca, this is just more reason to roll up its sleeves and get to negotiating with payers. Its head of China, Leon Wang, has previously told Bloomberg that he sees new treatments contributing to 60% of all its China revenue within five years.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
When FDA Requires Pediatric Studies for New Cancer Drug Submissions: New Draft Guidance [RAPS] The 13-page draft guidance explains how FDA will decide whether a molecular target is “substantially relevant to the growth or progression of pediatric cancer,” including information on waivers and deferrals.
Senate confirms Stephen Hahn, oncologist and political newcomer, as FDA commissioner [STAT] Hahn, who was most recently chief medical executive at MD Anderson Cancer Center in Houston, was confirmed 72-18. While he was able to garner significant Democratic support, that makes him one of the most contentious picks to lead the sprawling FDA in recent memory, despite the nominee’s apparent efforts to avoid controversy.
Stephen Hahn confirmed as new FDA chief [EndPoints] The MD Anderson exec, though, largely sailed through his confirmation hearings last month. Continually extolling the virtues of science, data and transparency, Hahn evaded firm answers on questions about drug pricing, opioids and e-cigarettes that have become issues of national debate.
	5.6.7 ESMO - IMMUNOTHÉRAPIES
Sitravatinib Plus Tislelizumab Show Promise in Platinum-Resistant Advanced Ovarian Cancer [ESMO] Novel combination of sitravatinib and tislelizumab shows manageable safety and promising activity in phase Ib study.
Early Introduction of Corticosteroids May Alter the Efficacy of Immune Checkpoint Inhibitors [ESMO] Two studies describe impact of the initiation of steroids early during the course of immune checkpoint inhibition on patient outcome.
	5.6.7.1 ESMO-IMMUNOTHÉRAPIES-PEMBROLIZUMAB
ESMO I-O: Keytruda shines among KRAS-mutated patients in Merck's latest lung cancer analysis [Fierce Pharma] The data help put aside “a question that has been asked a number of times,” especially as interest in KRAS—and candidates targeting KRAS, one type of RAS mutation—has mounted.
Data from Exploratory Analysis Show Merck’s KEYTRUDA® (pembrolizumab) Improved Overall Survival as Monotherapy for the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer Regardless of KRAS Mutational Status [Merck] The objective of the exploratory analysis was to assess the prevalence of KRAS mutations and their association with efficacy in the KEYNOTE-042 trial.
KRAS analysis vaults Merck's flagship Keytruda back into the spotlight [EndPoints] The jewel in Merck’s crown — Keytruda — just got more precious. On Thursday, the US drugmaker broke out an exploratory analysis showing the checkpoint inhibitor helped patients live longer as the first line of defense in patients with a form of non-small cell lung cancer (NSCLC) whose tumors expressed PD-L1, regardless of KRAS status.
Pembrolizumab May Be Considered as a First-Line Treatment Option in Non-Squamous NSCLC Even in the Presence of KRAS Mutations [ESMO] Efficacy of pembrolizumab alone or combined with chemotherapy is solid regardless of KRAS mutations in non-squamous non-small cell lung cancer.
	5.6.7.2 ESMO-IMMUNOTHÉRAPIES-NIVOLUMAB
ESMO I-O: BMS zooms in on squamous lung cancer patients as it dissects Opdivo-chemo combo failure [Fierce Pharma] “It’s difficult, it’s very difficult—and I would bring this from the point of the clinician who has to make a choice” between therapies—“to compare all the studies that are using … different antibodies and different subgroups of patients.”
First-line Nivolumab Plus Ipilimumab is Safe and Provides Encouraging Survival in Patients with Advanced NSCLC and Co-Morbidity or Poor Performance Status [ESMO] Nivolumab plus ipilimumab is effective regardless of PD-L1 expression levels in advanced NSCLC.
First-line Nivolumab Plus Chemotherapy Did Not Meet the Primary Endpoint of Overall Survival in Non-Squamous NSCLC [ESMO] Results of the CheckMate 227 - part 2 final analysis.
	5.7.1 SABCS-COMMUNIQUÉS
MINDACT Trial Data Reveal Certain Women With Luminal Breast Cancer May Be Undertreated With Tamoxifen Alone [SABCS] Cardoso and colleagues evaluated five-year DMFS among HR-positive, HER2-negative breast cancer patients enrolled in the MINDACT trial who had a low genomic risk and a high clinical risk and were randomized to receive chemotherapy based on either clinical or genomic risk.
Partial Breast Irradiation May be as Effective as Whole Breast Irradiation in Preventing Recurrence in Patients with Early Breast Cancer [SABCS] 10-year follow-up data supports earlier findings on recurrence and survival.
Combining Atezolizumab with Neoadjuvant Chemotherapy Does Not Improve Pathologic Complete Response Rates for Patients with TripleNegative Breast Cancer [SABCS] “Our observations may indicate that there is no therapeutic benefit to adding atezolizumab to neoadjuvant chemotherapy compared to chemotherapy alone, or it may simply mean that any beneficial effects of the combination will be seen in the long term,” said Gianni.
Neoadjuvant Treatment with Pembrolizumab Improves Pathologic Complete Response Rates for Patients with Triple-Negative Breast Cancer with Lymph Node Involvement [SABCS] Results on pCR rates from this trial were previously presented at the European Society of Medical Oncology annual meeting, held earlier this year. The latest data presented here included subgroup analyses of patients with lymph node involvement.
	5.7.2 SABCS-DIVERS
New Evidence From Large Studies Highlights Value Of Oncotype DX Breast Recurrence Score® To Guide Chemotherapy Treatment In Young Patients With Node-Negative Or Node-Positive Early-Stage Breast Cancer [Exact Sciences] New Publication of Long-term Data from Real-world Clinical Practice Confirms Conclusions of TAILORx.
	5.7.4 SABCS-ESSAIS
Puma Biotechnology Presents Results from the Phase II SUMMIT Trial of Neratinib for ERBB2 (HER2) Mutant, HER2 Non-Amplified, Metastatic Breast Cancer at the 2019 San Antonio Breast Cancer Symposium [Puma] The interim efficacy summary of the breast cohort that received neratinib in combination with trastuzumab and fulvestrant showed that for the 17 efficacy evaluable patients, 9 patients (53%) experienced a confirmed objective response, all of which were classified as partial responses, and 10 patients (59%) experienced clinical benefit (clinical benefit is defined as confirmed complete response or partial response or stable disease for at least 24 weeks).
	5.7.4.5 SABCS-ESSAIS-ANASTROZOLE
Breast Cancer Preventive Effects of Anastrozole Persist Long After Stopping Treatment [SABCS] “Our new data show that after a median of 10.9 years of follow-up there continues to be a significant reduction in breast cancer incidence.”
	5.7.4.6 SABCS-ESSAIS-IMMUNOTHÉRAPIES
Immunotherapy Regimens Yield Contrasting Results in Early Triple Negative Breast Cancer [Genome Web] Results also didn't paint a clear picture for the impact of PD-L1 status in this setting, reinforcing the challenge oncologists who want to practice precision medicine face with immunotherapy biomarkers that continue to vary across different drugs, cancers, and clinical niches.
SABCS: Merck's Keytruda notches win in triple-negative breast cancer as Roche's Tecentriq falls short [Fierce Pharma] While Keytruda didn't show a significant benefit over chemo in terms of preventing recurrence at this stage of the study, Baynes noted that achieving pathologic complete response was generally a "good predictor" that the disease wouldn't return.
	5.7.5 SABCS-BIOPSIES LIQUIDES
Blood test can quickly match advanced breast cancer patients to targeted treatments [Cancer Research UK] This new study looked at whether a blood test could detect three targetable defects in genes called HER2, ESR1 and AKT1, which are known to drive breast cancer.
	6. LUTTE CONTRE LES CANCERS
Quality Measurement in Oncology: Is the Race Worth Running? [Journal of Clinical Pathways] In some cases, dedicating more resources to improve quality measurement is the right way to go. In other cases—and even perhaps in most cases—abandoning quality measurement and trusting doctors judgement may be preferred.
	6.10.1 POLITIQUES (USA)
House passes drug pricing bill that pharma warned would bring 'nuclear winter' [Biopharma Dive] Even if, as appears likely, the bill backed by House Speaker Nancy Pelosi, D-Calif., will never be signed into law, today's vote was still significant. Years of lobbying and public pressure have forced lawmakers to act and has knocked the pharmaceutical industry on its heels.
House passes major drug-pricing bill, a Democratic salvo in a showdown far from over [STAT] President Trump has vowed he would veto the bill, which passed on a 230-192 vote, largely along party lines. The Senate is still considering a separate, less aggressive bipartisan drug pricing package.
	6.3 ASSOCIATIONS/FONDATIONS
Who cares for the carers? The charity providing vital support for the partners of cancer patients [The Telegraph] Leukaemia Care takes “caring for carers” seriously. It offers practical information, from carer’s allowances to their legal rights as an employee – but it also has advice for dealing with the emotional toll of becoming a carer to a leukaemia patient.
	6.7.1 IA/BIOINFORMATIQUE
Machine learning for clinical decision-making: pay attention to what you don’t see [STAT] In our drive to improve health with (and without) machine learning, we must not forget to look for what is missing: What information do we not have about the underlying health care system? Why might an individual or a code be unobserved? What subgroups have not been prioritized? Who is on the research team?