Hanno curato la selezione degli articoli scientifici e i commenti di questo numero:Ugo De Giorgi, Chiara Casadei, Giuseppe Schepisi (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRST, IRCCS Meldola, FC)
Coordinatori: Massimo Di Maio, Silvia Novello
Editore: Intermedia – Direttore Responsabile: Mauro Boldrini
Oggi in Oncologia
Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA
Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were … (leggi tutto)
In un recente articolo apparso sulla pagina online della rivista Annals of Oncology, un team di ricercatori sotto la guida del Dr Michael Seiden, Presidente di US Oncology (Texas, USA), ha sviluppato un sistema in grado di detettare su sangue periferico più di 50 tipi di neoplasia e sua origine, anche in fase precoce ossia prima che ci siano segni o sintomi clinici della patologia.
Questo sotto-studio prospettico caso-controllo ha valutato le prestazioni dell’analisi di metilazione mirata del DNA libero da cellule circolanti (cfDNA) per rilevare e localizzare più tipi di cancro, in tutte le fasi, ad alta specificità.
I 6.689 partecipanti [2.482 pazienti oncologici (> 50 tipi di cancro), 4.207 non affetti da neoplasia] sono stati divisi in set di training e validazione. Il cfDNA è stato sottoposto a sequenziamento del bisolfito indirizzato a un pannello di > 100.000 regioni di metilazione. È stato sviluppato e validato un classificatore per la rilevazione del cancro e la localizzazione del tessuto di origine.
I risultati ottenuti sono stati coerenti nei set di training e convalida. Nella validazione, la specificità era pari al 99,3% [intervallo di confidenza (IC) al 95%: 98,3% – 99,8%; tasso di falsi positivi (FPR) 0,7%]. La sensibilità agli stadi I-III era del 67,3% (IC: 60,7% – 73,3%) in un set predefinito di 12 tipi di cancro (ano, vescica, colon / retto, esofago, testa e collo, fegato / dotto biliare, polmone, linfoma, ovaio, pancreas, stomaco), che rappresentano ogni anno il 63% circa dei decessi per cancro negli Stati Uniti ed era del 43,9% (IC: 39,4% – 48,5%) in tutti i tipi di cancro. La capacità di rilevamento aumentava con il peggioramento dello stadio di malattia: nei tipi di cancro pre-specificati la sensibilità era del 39% (IC: 27% – 52%) nello stadio I, 69% (IC: 56% – 80%) nello stadio II, 83% (IC: 75% – 90%) nel III e 92% (IC: 86% – 96%) nello stadio IV. In tutti i tipi di tumore la sensibilità era del 18% (IC: 13% – 25%) nello stadio I, 43% (IC: 35% – 51%) nello stadio II, 81% (IC: 73% – 87%) nello stadio III e 93% (IC: 87% – 96%) nello stadio IV.
Il sequenziamento di cfDNA sfruttando i modelli di metilazione informativa ha rilevato più di 50 tipi di cancro. Sicuramente la metodica andrà validata prospetticamente anche per meglio esplorare le sue potenzialità nell’ambito della diagnosi precoce.
Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer
Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. A prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV- … (leggi tutto)
I 5 tipi di papillomavirus umano (HPV) ad alto rischio (16, 18, 31, 33 e 35) rappresentano la principale causa di numerose neoplasie tra cui il carcinoma squamo-cellulare dell’orofaringe, della cervice e dell’ano. In particolare, negli ultimi anni il carcinoma squamo-cellulare dell’orofaringe (oropharyngeal squamous cell carcinoma, OPSCC) ha registrato un importante aumento di incidenza. L’outcome per questo tipo di neoplasia è più favorevole rispetto a quello dell’OPSCC HPV-negativo; tuttavia, circa il 10-25% dei pazienti è destinato a sviluppare una recidiva della malattia.
In questo studio prospettico, gli autori hanno sottoposto 115 pazienti con diagnosi di OPSCC HPV-positivo, precedentemente trattati con regime chemio-radioterapico a intento curativo, a follow-up secondo le linee guida del National Comprehensive Cancer Network (NCCN). Inoltre, ogni 6 – 9 mesi veniva raccolto un campione di sangue per determinare la presenza di ctHPVDNA (plasma circulating tumor human papillomavirus DNA). Obiettivo primario dello studio era quello di definire il valore predittivo negativo (VPN) e positivo (VPP) del test.
Dopo un follow-up mediano di 23 mesi, 15 pazienti (13%) avevano sviluppato una recidiva di malattia. In 87 pazienti non era stato riscontrato ctHPVDNA in nessuno dei prelievi eseguiti e in nessuno di loro era stata documentata una recidiva di malattia (VPN 100%; IC 95%: 96% – 100%). Ventotto pazienti avevano sviluppato un ctHPVDNA durante il follow-up, di cui sedici avevano avuto due prelievi consecutivi positivi. Per 15 di loro la biopsia aveva documentato una recidiva di malattia. Due riscontri consecutivi di ctHPVDNA hanno pertanto dimostrato di avere un VPP del 94% (IC 95%: 70% – 99%). Il prelievo ematico ha anticipato la biopsia, nel riscontro di recidiva, di 3,9 mesi.
Nel follow-up che segue la fine del trattamento curativo, il riscontro di due consecutivi ctHPVDNA nel plasma dei pazienti, sembra quindi avere un elevato VPN e VPP nell’identificare recidiva di OPSCC HPV-positivo, facilitando e anticipando l’avvio di una terapia di salvataggio.
Guidance on regulatory requirements in the context of the COVID-19 pandemic
April 10, 2020 – The European Commission, EMA and the European medicines regulatory network have developed a question-and-answer (Q&A) document to provide guidance to stakeholders on adaptations to the regulatory framework to address challenges arising from the COVID-19 pandemic, with a particular focus on crucial medicines for use in COVID-19 patients. The current pandemic is a global public health emergency causing major disruptions … (leggi tutto)
Update on EU actions to support availability of medicines during COVID-19 pandemic
April 10, 2020 – The continued availability of medicines is one of the most important priorities for EU authorities that are adopting measures to mitigate possible disruptions to the supply of medicines caused by the ongoing COVID-19 pandemic. The EU Executive Steering Group on Shortages of Medicines Caused by Major Events met virtually on 8 April to discuss ongoing activities aimed at ensuring a coordinated response to the challenges posed by the … (leggi tutto)
EMA establishes task force to take quick and coordinated regulatory action related to COVID-19 medicines
April 9, 2020 – As part of its health threat plan activated to fight COVID-19, the Agency has finalised and published the PDF iconcomposition and objectives of its COVID-19 EMA pandemic Task Force (COVID-ETF), which assists Member States and the European Commission in dealing with development, authorisation and safety monitoring of therapeutics and vaccines intended for treatment or prevention of COVID-19. The main purpose of the COVID-ETF is … (leggi tutto)
Global regulators discuss observational studies of real world data for COVID-19 medicines
April 7, 2020 – In a dedicated COVID-19 workshop, organised by the European Medicines Agency (EMA) under the umbrella of the International Coalition of Medicines Regulatory Authorities (ICMRA), international regulators discussed how data generated during clinical practice could complement evidence from clinical trials with potential therapeutics or vaccines against COVID-19. Participants from more than 25 countries, representing 28 medicines … (leggi tutto)
Brigatinib Approved in Europe for Frontline ALK+ NSCLC
April 6, 2020 – The European Commission has approved brigatinib for the first-line treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC). The approval is based on the phase III ALTA-1L trial, in which treatment with brigatinib demonstrated a 57% reduction in the risk of disease progression or death compared with crizotinib in patients with advanced ALK-positive NSCLC who had not received a prior ALK inhibitor. Two-year investigator- … (leggi tutto)
Protecting Medical Staff to Ensure Cancer Patients can Safely Receive Care during the Pandemic
April 6, 2020 – As the proportion of healthcare workers with COVID-19 has rapidly increased in many countries since the beginning of the outbreak, implementing efficient measures to protect medical teams has become a top priority globally, with clear benefits for the quality of care in oncology too. According to Antonio Passaro, from the European Institute of Oncology (IEO) in Milan, Italy, protecting medical oncologists from contracting the virus is key to … (leggi tutto)
No Change to Product Information for Lapatinib Following Re-Assessment of Data
April 6, 2020 – On 27 March 2020, the European Medicines Agency (EMA) announced that the product information for lapatinib will continue to state that no data are available on the effectiveness of lapatinib used together with an aromatase inhibitor compared with trastuzumab used with an aromatase inhibitor in breast cancer patients previously treated with trastuzumab. In July 2018, results of a study involving women with hormone receptor … (leggi tutto)
Avelumab sBLA Filed for Frontline Maintenance in Urothelial Carcinoma, Breakthrough Designation Granted
April 9, 2020 – A supplemental Biologics License Application (sBLA) has been filed with the FDA for avelumab for the frontline maintenance treatment of patients with locally advanced or metastatic urothelial carcinoma, according to EMD Serono (Merck KGaA) and Pfizer, the codevelopers of the PD-L1 inhibitor. The sBLA and breakthrough designation are based on findings from the phase III JAVELIN Bladder 100 study (NCT02603432), in which … (leggi tutto)
FDA Approves Encorafenib/Cetuximab Combo for BRAF+ mCRC
April 8, 2020 – The FDA has approved the combination of encorafenib and cetuximab for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. The approval is based on findings from the phase III BEACON CRC study, which evaluated encorafenib plus cetuximab with or without binimetinib (Mektovi) in this patient population. Results showed that both the doublet and … (leggi tutto)
FDA Grants Nivolumab/Ipilimumab Plus Chemo Priority Review in Frontline NSCLC
April 8, 2020 – The FDA has granted a priority review designation to nivolumab plus ipilimumab and chemotherapy for use as a frontline treatment for patients with metastatic or recurrent non–small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations. The application for the regimen is based on findings from the phase III CheckMate-9LA trial, in which nivolumab plus low-dose ipilimumab given concomitantly with 2 cycles of chemotherapy … (leggi tutto)
FDA Grants Balstilimab Fast Track Designation for Cervical Cancer
April 7, 2020 – The FDA has granted balstilimab a Fast Track Designation for the treatment of patients with cervical cancer, according to Agenus, the manufacturer of the PD-1 inhibitor. The designation, which will expedite the review of balstilimab in this setting, is the second fast track designation for the agent. Last month, the FDA granted a Fast Track designation to the combination of balstilimab and the CTLA-inhibitor zalifrelimab for the treatment of patients with … (leggi tutto)
FDA Grants Sacituzumab Govitecan Fast Track Designation for Urothelial Carcinoma
April 7, 2020 – The FDA has granted a fast track designation to the antibody-drug conjugate (ADC) sacituzumab govitecan for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor, and a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, including patients who are platinum ineligible and have previously received a PD-1/PD-L1 … (leggi tutto)
FDA Grants Pembrolizumab Priority Review for TMB-High Tumors
April 7, 2020 – The FDA has granted a priority review designation to pembrolizumab for the treatment of patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) status (≥10 mutations / megabase), as determined by an FDA-approved test, who have progressed following prior treatment and who have no satisfactory alternative treatment options. The pembrolizumab application is based in part on the … (leggi tutto)
Clinical Trials to Evaluate Activity of Biologics, Other Agents Against COVID-19
April 6, 2020 – In an effort to expedite research for agents with potential activity against symptoms associated with the novel coronavirus (COVID-19), the U.S. Food and Drug Administration (FDA) is evaluating and/or has approved a number of randomized clinical trials seeking to determine whether a drug has activity in this disease setting. The FDA has approved a randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the safety and … (leggi tutto)
Sacituzumab Govitecan Succeeds in Phase III TNBC Trial, as FDA Weighs Approval
April 6, 2020 – The confirmatory phase III ASCENT study exploring sacituzumab govitecan in patients with metastatic triple-negative breast cancer (TNBC) has been stopped due to “compelling evidence of efficacy,” according to a statement from the company developing the antibody-drug conjugate (ADC), Immunomedics. The company halted the trial based on a unanimous recommendation from the independent Data Safety Monitoring Committee (DSMC) … (leggi tutto)
COVID-19 Causes Shifts in Clinical Trial Practices
April 12, 2020 – The increasing severity of the COVID-19 pandemic has prompted shifts in the treatment of patients with cancer, according to Shilpa Gupta, MD, with some patients delaying therapy to avoid potential exposure to the virus and clinical trials being put on hold until further notice. At Cleveland Clinic, healthcare personnel are working to transition over to virtual visits whenever possible so that patients can avoid unnecessary exposure to the virus … (leggi tutto)
New COVID-19 Cancer Registry Aims to Understand Impact on Patients During Pandemic, Inform Future Care
April 10, 2020 – The American Society of Clinical Oncology (ASCO) today launched the ASCO Survey on COVID-19 in Oncology Registry (ASCO Registry) to help the entire cancer community learn about the pattern of symptoms and severity of COVID-19 among patients with cancer, as well as how COVID-19 infections impact the delivery of cancer care and patient outcomes. The registry will collect both baseline and follow up data throughout the COVID-19 … (leggi tutto)
New Guidance Released for Oncology Community on Allocation of Limited Resources During COVID-19 Pandemic
April 9, 2020 – The American Society of Clinical Oncology (ASCO) today released a set of recommendations to support the oncology community as health care institutions across the United States face potentially difficult decisions around the allocation of scarce health care resources during the COVID-19 pandemic. In some geographic areas, the ongoing crisis is expected to demand more resources – including ventilators, critical and intensive care beds … (leggi tutto)
NCCN Publishes COVID-19 Safety Recommendations for Oncology Community
April 9, 2020 – Although efforts to “flatten the curve” are showing some signs of hope, the COVID-19 crisis continues to present major challenges to the oncology community. To assist with these issues, the National Comprehensive Cancer Network (NCCN) has published guidelines for ensuring that patients with cancer, care providers, and staff are kept as safe as possible during the crisis. “The unprecedented challenges we are all facing from the COVID-19 … (leggi tutto)
AACR Annual Meeting 2020 to Be Held in a Virtual-Only Format
April 6, 2020 – Today, the American Association for Cancer Research (AACR) Board of Directors issued the following announcement: The AACR has been closely monitoring the rapid escalation of the COVID-19 pandemic. The health and safety of all Annual Meeting attendees and the patients and communities they serve are the AACR’s highest priorities. Therefore, the AACR Board of Directors has made the decision not to move forward with an … (leggi tutto)
Gilteritinib Takes Step Toward Chinese Approval for FLT3+ AML
April 10, 2020 – The China National Medical Products Administration (NMPA) has accepted a New Drug Application (NDA) for gilteritinib for the treatment of adult patients with FLT3 mutation–positive, relapsed/refractory acute myeloid leukemia (AML). The efficacy of gilteritinib in this setting was demonstrated in the phase III ADMIRAL trial, which demonstrated an improvement in overall survival (OS) with the FLT3 inhibitor compared with salvage chemotherapy … Leggi tutto
11 aprile 2020 – COVID-19 – scheda informativa AIFA su eparine a basso peso molecolare
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