Onco Actu du 3 avril 2017

	5. Traitements
How Cancers Evolve Drug Resistance [The Scientist] Researchers unravel the sophisticated ways cancers evade treatments, including immunotherapies, designed to destroy them.
	5.10 Traitements - Essais
Draft guideline on multiplicity issues in clinical trials [EMA] This guideline is intended to provide guidance on how to deal with multiple comparison and control of type I error in the planning and statistical analysis of clinical trials. From the points to consider document published in 2002, aspects related with multiplicity issues in safety, drug-response studies, secondary endpoints, subgroup analysis and estimation were added or updated, and statistical terms were clarified.
	5.12 Immunothérapies
CT Scans May Offer a Non-invasive Alternative to Diagnose Immunotherapy-induced Colitis [AACR] To assess whether CT scans can provide a safer, faster, and more cost-effective alternative to reliably diagnose colitis, Ott and colleagues retrospectively assessed 303 patients with metastatic melanoma who had been treated with ipilimumab at DFCI between 2008 and 2015.
More Biomarkers Needed for Cancer Immunotherapy [The Scientist] Measuring PD-L1 levels was a great start. Now we need to quantify more protein biomarkers, assess the tumor mutational landscape, and examine immune cell signatures, too.
Neoantigens Enable Personalized Cancer Immunotherapy [The Scientist] Tumors’ mutations can encode the seeds of their own destruction, in the form of immunogenic peptides recognized by T cells.
Promising cancer drugs may speed tumours in some patients [Nature] Early studies fuel scientists’ determination to understand how immunotherapy may sometimes make disease worse.
	5.12.1 Immunothérapies - partenariats
Bristol-Myers Squibb and Incyte to Advance the Combination of Opdivo (nivolumab) and Epacadostat into First-line Registrational Trials [BMS] Companies to initiate Phase 3 registrational trials in first-line non-small cell lung cancer across the spectrum of PD-L1 expression and first-line head and neck cancer in 2017.
Merck, Incyte map a Phase III pipeline of their own for a frontline combo of Keytruda and epacadostat [EndPoints] Merck, of course, is sparing no expense in pushing dozens of pivotal studies of Keytruda, intent on capitalizing on a major market opportunity and unwilling to let a growing field of competitors hamper its pursuit of blockbuster revenue.
	5.12.2 Immunothérapies - CAR-T
Making CAR T-Cell Therapy Safer [The Scientist] Following a spate of patient deaths in clinical trials testing modified T cells for the treatment of cancer, researchers work to reduce the treatment’s toxicity without sacrificing efficacy.
Kite Pharma hits its Q1 deadline on filing a BLA for its pioneering CAR-T, posts improved data [EndPoints] The move puts Kite one step behind Novartis, which two days ago announced that it had the FDA’s commitment for a speedy review of its own CAR-T.
	5.2 Pharma
Phase III ALUR study supports the use of Roche’s Alecensa for people with advanced ALK-positive lung cancer [Roche] The peer-reviewed data will be published later this year.
	5.2.3 Pharma - économie
Halozyme dips after pancreatic cancer trial halted for futility [FierceBiotech] The failure of the investigator-initiated trial to show signs of efficacy raised doubts about the ability of PEGPH20 to deliver positive data in phase 3, despite differences in the designs of the studies.
Halozyme slides on an early futility failure for its lead cancer therapy [EndPoints] Investigators were using a combination of PEGPH20 plus Folfirinox against Folfirinox alone on previously untreated metastatic pancreatic cancer, a tough challenge for any drug. Now the San Diego-based biotech has halted enrollment as it analyses the data.
	5.3.4 Traitements - AMM (FDA, EMA)
IBRANCE® (palbociclib) Receives FDA Regular Approval and Expanded Indication for First-Line HR+, HER2- Metastatic Breast Cancer [Pfizer] IBRANCE is the first CDK 4/6 inhibitor approved by the FDA.
Novartis drug combination Tafinlar® + Mekinist® receives EU approval for BRAF V600-positive advanced non-small cell lung cancer (NSCLC) [Novartis] The approval marks the first targeted treatment approved for the patient population, who previously had few treatment options, in all 28 member states of the European Union (EU), plus Iceland and Norway.
FDA Approves New PARP Inhibitor for Ovarian Cancer [Cancer Research Catalyst] Niraparib is the third in a class of molecularly targeted therapeutics called poly ADP-ribose polymerase (PARP) inhibitors to be approved by the FDA. However, it is the first to be approved for use in treating both BRCA mutation–positive and –negative cancers.
	5.9 AACR
Aggressive breast cancer grows faster in obese environment [UNC Lineberger] For the study, researchers in the Makowski lab studied a type of breast cancer known as triple-negative breast cancer. Researchers transplanted and grew triple negative breast cancer cells from lean laboratory models into models of obese, lean and formerly obese microenvironments to observe how tumors grew in these different contexts.
Drug combination boost PARP inhibitor response in resistant ovarian cancer [Dana-Farber Cancer Institute] Twenty-eight patients with high-grade serous ovarian cancer received olaparib, a PARP inhibitor, along with an investigational alpha-specific PI3-Kinase inhibitor, BYL719, in the phase I trial. Twenty-six of the 28 had platinum-resistant cancer.
Beyond genomics: Using proteomics to target tumors [Fred Hutch] Dr. Amanda Paulovich, whose lab has a leading role in the Beau Biden Cancer Moonshot, will speak at the AACR annual meeting about her lab’s pioneering methods to measure proteins that serve as tumor markers.
Phase II Copanlisib Data Show Durable Tumor Response in Indolent Non-Hodgkin’s Lymphoma [Bayer] Copanlisib achieves objective tumor response rate of 59% in indolent Non-Hodgkin’s Lymphoma (iNHL) patients with a manageable safety profile in CHRONOS-1 study.
A ‘sci-fi’ cancer therapy fights brain tumors, study finds [STAT] Many doctors are skeptical of the therapy, called tumor treating fields, and it’s not a cure. It’s also ultra-expensive — $21,000 a month.
Combination HER2-targeted Therapy Effective in Heavily Pretreated HER2-positive Colorectal Cancer Patients [AACR] At data cutoff (February 28, 2017), 10 of the 33 patients in cohort A achieved an objective response, which included two complete responses and eight partial responses; 13 had stable disease. Six patients experienced grade 3 adverse events.
Wearable Medical Device Improves Survival for Patients with Glioblastoma [AACR] TTFields are low-intensity electric fields alternating at an intermediate frequency (200kHz) that are thought to exert anticancer effects by blocking cell division, explained Stupp. For patients with glioblastoma, the TTFields are delivered continuously to the brain by a patient-operated, wearable medical device.
Targeted Therapies Selected Based on Multigene Panel Improved Outcomes for Patients with Hard-to-treat Cancers [AACR] Limitations of the study include that this was not a randomized trial; therefore, the outcomes from patients who received targeted therapies could not be compared with the outcomes from those who received nontargeted therapies or with the outcomes from patients with similar disease but without the matched genomic alterations, André said.
Cancer Type and Mutation Identity Influenced Response to Targeted Therapy in a Basket Clinical Trial [AACR] The take-home message at this point is that there are areas of promise, but we will likely need to combine pan-HER inhibition with other treatment modalities, such as chemotherapy or antihormone therapy, in order to obtain practice-changing response rates and durability of response.
	6. Lutte contre les cancers
NHS England sets target of 5,000 more people each year surviving cancer [Cancer Research UK] The report sets out a number of measures to achieve this target, including investment in new radiotherapy machines, support for services to diagnose cancers earlier, and personalised care for patients.
Contrary to what we are frequently told, we are not “losing the war on cancer” [Science-Based Medicine] It might have been hubris to think that progress would be anything other than slow, or it might have been overpromising in order to secure research funding. It was probably both. Whatever the case, conquering all cancers is a project that will take more than decades. It will take generations.
	6.1 Observation
Annual Report to the Nation: Cancer death rates continue to decline [NCI] Compared to cases diagnosed in 1975-1977, five-year survival for cancers diagnosed in 2006-2012 increased significantly for all but two types of cancer: cervix and uterus.
ASCO Statement on the Annual Report to the Nation on the Status of Cancer, 1975-2014 [ASCO] America’s federal investment in biomedical research has fueled discoveries and insights that help us better prevent, diagnose, and treat cancer. The more than 15 million cancer survivors alive today are living proof that this investment pays major dividends.
US cancer death rates continue to fall as 5-year survival rates rise – study [The Guardian] Death rates from 2010 to 2014 decreased for 11 of the 16 most common types of cancer in men and for 13 of the 18 most common types of cancer in women, including lung, colorectal, female breast, and prostate cancers.
	6.10.1 Politiques (USA)
Should taxpayers cover the light bills at university labs? Trump kicks off a tense debate [STAT] Funding for overhead costs at labs has been a source of controversy — and, on some campuses, resentment — for years.
	6.11 Patients
Cancer patients have 55% greater risk of suicide, study finds [The Guardian] Co-author Dr Raffaella Calati from the department of emergency psychiatry and post-acute care at Lapeyronie hospital, Montpellier, described the results, derived by pooling data from 15 studies, as “extremely preliminary” but nevertheless significant.
Cancer patient's family stands to lose £50k under benefit cuts [The Guardian] “My death, on or before Thursday, changes my family’s wellbeing to the tune of tens of thousands. It is utterly unbelievable.” Alan’s voice cracked, not just with emotion but the brutal impact of four years of cancer that started in a tonsil before spreading to his lungs and chest, delivering a terminal diagnosis in June, 2015.
	6.6 Publications
NIH’s new embrace of preprints will be a boon to science [STAT] In what is “likely a watershed moment for preprints in the life sciences,” the NIH this month announced a new policy of encouraging researchers it funds to submit their work to preprint servers before they attempt to publish in conventional journals.