Hanno curato la selezione degli articoli scientifici e i commenti di questo numero: Oronzo Brunetti, Nicola Silvestris (Università degli Studi di Bari, Istituto Tumori “Giovanni Paolo II”, Bari)
Coordinatori: Massimo Di Maio, Silvia Novello
Editore: Intermedia – Direttore Responsabile: Mauro Boldrini
Oggi in Oncologia
Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial
The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of … (leggi tutto)
La tripletta FOLFOXIRI (fluorouracile, acido folinico, oxaliplatino e irinotecan) in associazione al bevacizumab ha già un vantaggio netto in termini di tasso di risposta, sopravvivenza libera da progressione (PFS) mediana e sopravvivenza, sebbene associato ad un incrementato rischio di tossicità per i pazienti affetti da carcinoma del colon-retto metastatico, rispetto alla combinazione FOLFIRI (fluorouracile, acido folinico e irinotecan) più bevacizumab in prima linea.
Restava da chiarire il dubbio dell’efficacia di una seconda linea di trattamento al momento del fallimento della tripletta.
Nello studio TRIBE2, i pazienti (di età compresa tra 18 e 75 anni con uno status performance ECOG pari a 2) con adenocarcinoma del colon avanzato e malattia non resecabile sono stati randomizzati a ricevere FOLFOXIRI+bevacizumab per un massimo di 8 cicli (seguito da mantenimento FUFA+bevacizumab) e reintroduzione dello stesso schema al momento della prima progressione vs FOLFOX+bevacizumab per un massimo di 8 cicli (seguito da mantenimento) e seconda linea con FOLFIRI+bevacizumab al momento della prima progressione.
L’endpoint primario era la PFS2, definita come il tempo che intercorre tra la randomizzazione e la progressione della malattia in qualsiasi trattamento somministrato dopo la prima progressione della malattia o la morte del paziente.
Nello studio sono stati arruolati 679 pazienti (340 nel gruppo di controllo e 339 nel gruppo sperimentale). La PFS2 è stata di 19,2 mesi (IC 95%: 17,3-21,4) nel gruppo sperimentale e 16,4 mesi (IC 95%: 15,1-17,5) nel gruppo di controllo (HR 0,74; IC 95%: 0,63-0,88; p = 0,0005). Durante il trattamento di prima linea, il più frequente degli eventi di grado 3-4 per tutte le cause sono stati diarrea 57 [17%] vs 18 [5%] pazienti, neutropenia 168 [50%] vs 71 [21%] pazienti, e ipertensione arteriosa 25 [7%] contro 35 [10%] pazienti nel gruppo sperimentale rispetto al gruppo di controllo. Sono stati segnalati otto decessi correlati al trattamento nel gruppo sperimentale e quattro nel gruppo di controllo. Dopo la prima progressione della malattia, non sono state riportate differenze sostanziali nell’incidenza di eventi avversi di grado 3 o 4 tra il gruppo di controllo e quello sperimentale, ad eccezione della neurotossicità, che è stata riportata solo nel 5% del gruppo sperimentale. Eventi avversi gravi dopo la progressione della malattia si sono verificati nel 15% dei pazienti nel gruppo sperimentale e nel 12% del gruppo di controllo. Tre decessi correlati al trattamento dopo la prima progressione della malattia sono stati riportati nel gruppo sperimentale e quattro nel gruppo di controllo.
Da questo studio emerge come FOLFOXIRI+bevacizumab iniziale, seguito dalla reintroduzione dello stesso regime dopo la progressione della malattia, sembra essere una strategia terapeutica preferibile alla somministrazione sequenziale di doppietti chemioterapici, in combinazione con bevacizumab, per pazienti con carcinoma del colon-retto metastatico. Inoltre, sembrerebbero essere sufficienti 4 mesi di trattamento upfront prima del mantenimento con FUFA e bevacizumab. Infine si consolida il dato che la scelta terapeutica della tripletta, ripresa a progressione dopo il mantenimento, è la strategia più indicata nei pazienti con buon ECOG, candidati a terapia massimale, soprattutto se con tumore localizzato a destra o mutato.
Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial
Pembrolizumab plus pemetrexed-platinum led to superior overall survival and progression-free survival, and a higher proportion of patients with a confirmed complete or partial response over placebo plus pemetrexed-platinum in the KEYNOTE-189 study. We aimed to evaluate prespecified exploratory patient-reported outcomes (PROs) in patients in KEYNOTE-189. In the multicentre, double-blind, randomised, placebo-controlled, phase 3 … (leggi tutto)
Lo studio KEYNOTE-189 era uno studio multicentrico, in doppio cieco, randomizzato di fase 3, condotto presso 126 centri di cancro in 16 Paesi, pazienti idonei di età pari o superiore a 18 anni con metastatica non squamosa confermata istologicamente o citologicamente EGFR o ALK non mutati. Nello studio KEYNOTE-189, l’aggiunta del pembrolizumab alla combinazione platino/pemetrexed ha portato ad un incremento della sopravvivenza globale e della sopravvivenza libera da progressione (PFS) con una percentuale maggiore di pazienti con una risposta completa o parziale.
In questa analisi, pubblicata su Lancet Oncology, sono stati valutati i questionari sulla qualità di vita, in particolare il QLQ-C30 e un questionario specifico del cancro del polmone, il QLQ-LC13. Tali questionari sono stati compilati dai pazienti ai cicli 1-5, e successivamente ogni tre cicli durante il primo anno e ogni quattro cicli durante i due anni successivi. Gli endpoint chiave di quest’analisi erano il cambiamento della qualità di vita dal basale alla dodicesima settimana (ovvero durante la chemioterapia) e alla ventunesima settimana (dopo la chemioterapia) valutando lo stato di salute globale/qualità della vita (GHS/QOL) e il tempo al deterioramento sintomatico, includendo tosse, dolore al torace o dispnea.
Al basale, 359 (89%) su 402 pazienti nel gruppo pembrolizumab più pemetrexed/platino e 180 (90%) su 200 nel gruppo placebo più pemetrexed/platino avevano completato i questionari. Alla dodicesima settimana, 319 (90%) di 354 nel gruppo sperimentale e 149 (89%) di 167 pazienti nel gruppo controllo l’avevano compilato; alla ventunesima settimana, 249 (76%) di 326 nel primo gruppo e 91 (64%) di 143 nel secondo gruppo l’avevano consegnato. Al basale e alla dodicesima settimana, in entrambi i gruppi, circa il 90% aveva compilato il questionario, successivamente l’aderenza alla compilazione si è ridotta.
Dal basale alla dodicesima settimana, i punteggi GHS/QOL sono stati mantenuti sia con pembrolizumab che con pemetrexed-platino quasi invariati. Dal basale alla ventunesima settimana, i punteggi GHS/QOL erano migliori nei pazienti sottoposti a pembrolizumab più pemetrexed-platino. Inoltre, il tempo mediano al deterioramento dei sintomi non era stato raggiunto nel braccio sperimentale (IC 95%: 10,2 mesi – non raggiunto), mentre era di 7 mesi nel braccio controllo (IC 95%: 4,8 mesi – non raggiunto) (HR 0,81; IC 95%: 0,60–1,09; p = 0,16).
In definitiva, l’aggiunta di pembrolizumab alla chemioterapia standard ha mantenuto GHS/QOL durante il trattamento chemioterapico, con punteggi GHS/QOL migliorati alla ventunesima settimana nel gruppo pembrolizumab più chemioterapia rispetto al gruppo placebo più chemioterapia.
Questi dati supportano ulteriormente l’uso di pembrolizumab più pemetrexed-platino come terapia di prima linea per i pazienti con carcinoma polmonare metastatico non a piccole cellule non squamoso e non EGFR/ALK mutato (pur con la ‘limitazione italiana’ di una prescrivibilità dettata da espressione di PD-L1).
In Europa
EMA provides recommendations on compassionate use of remdesivir for COVID-19
April 3, 2020 – During an extraordinary virtual meeting held on 2 April 2020, EMA’s human medicines committee (CHMP) gave recommendations on how the investigational antiviral medicine remdesivir should be used for treating coronavirus disease (COVID-19) in compassionate use programmes in the European Union. Compassionate use programmes, which are set up at the level of individual EU Member States, are intended to give patients with a … (leggi tutto)
International regulators discuss available knowledge supporting COVID-19 medicine development
April 3, 2020 – On 2 April, regulators from around the world joined the second workshop on COVID-19 organised by the European Medicines Agency (EMA) under the umbrella of the International Coalition of Medicines Regulatory Authorities (ICMRA). Participants from more than 25 countries, representing 28 medicines regulatory authorities globally and experts from the World Health Organization and the European Commission discussed the available … (leggi tutto)
Protecting Patients with Cancer Against Severe Covid-19 Disease in France
April 3, 2020 – On 25 March 2020, a group of medical and radiation oncologists from the academic and private settings in France, reported in The Lancet Oncology that based on request of the French Ministry of Health, the French High Council for Public health tasked them to prepare guidelines to protect patients with cancer against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while ensuring the continuum of cancer treatment … (leggi tutto)
Rituximab Biosimilar PF-05280586 Approved in Europe
April 2, 2020 – The European Commission (EC) has approved the rituximab biosimilar PF-05280586 for the treatment of patients with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris. In making its decision, the EC reviewed a comprehensive data package demonstrating biosimilarity with PF-05280586 to reference … (leggi tutto)
Improving Telemedicine Helps to Minimise Risks for Cancer Patients
April 2, 2020 – Virtual visits may provide a solution to a very real problem in oncology during the COVID-19 pandemic, when safety measures to contain the infection spread involve a reduction in the number of cancer patients visiting hospitals and outpatient clinics. To ensure continuity of cancer services and assistance to their patients, oncology teams in different countries are currently implementing or improving telemedicine services, to be integrated into … (leggi tutto)
Covid-19 Infection and Related Challenges in Aviano Cancer Centre in Italy
April 1, 2020 – The safety and management of cancer patients in the current SARS-CoV-2 outbreak is an important clinical concern. Most cancer clinics have established or are in the living process of adapting already established contingency plans. It is well known that patients with cancer are more susceptible to infections because of the immunosuppression. First reports from China indicate that developing severe events in COVID-19 disease is statistically significantly … (leggi tutto)
Immunotherapy Biomarker Testing Depends on Tumor Type
April 1, 2020 – Since the first tumor-agnostic immunotherapy was approved in 2017, questions about optimal procedures for biomarker testing have become more pressing. A Working Group of the European Society for Medical Oncology (ESMO) has determined that a decision tree on the sequential use of different tests in immunotherapy decision-making cannot be a general one for all cancers but should be designed on the basis of the specific tumor type … (leggi tutto)
COVID-19: chloroquine and hydroxychloroquine only to be used in clinical trials or emergency use programmes
April 1, 2020 – Chloroquine and hydroxychloroquine, two medicines currently authorised for malaria and certain autoimmune diseases, are being investigated worldwide for their potential to treat coronavirus disease (COVID-19). However, efficacy in treating COVID-19 is yet to be shown in studies. It is very important that patients and healthcare professionals only use chloroquine and hydroxychloroquine for their authorised uses or as part of clinical trials or … (leggi tutto)
EU recommendations for 2020/2021 seasonal flu vaccine composition
April 1, 2020 – EMA has issued the recommendations for the influenza virus strains that vaccine manufacturers should include in vaccines for the prevention of seasonal influenza from autumn 2020. Manufacturers of egg-based or live attenuated trivalent vaccines for the 2020/2021 season should include these three virus strains: an A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus; an A/Hong Kong/2671/2019 (H3N2)-like virus … (leggi tutto)
Brentuximab Vedotin Approaches European Approval for Frontline ALCL
March 31, 2020 – The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of brentuximab vedotin for use in combination with chemotherapy for the frontline treatment of adult patients with systemic anaplastic large cell lymphoma (sALCL). The recommendation, which is specifically for the use of the antibody-drug conjugate in combination with CHP (cyclophosphamide, doxorubicin … (leggi tutto)
Advancing regulatory science in the EU – new strategy adopted
March 31, 2020 – EMA has published its Regulatory Science Strategy to 2025 today. The strategy provides a plan for advancing regulatory science over the next five years, covering both human and veterinary medicines. It comes in response to the dramatic acceleration of the pace of innovation in recent years and the need for regulators to be ready to support the development of increasingly complex human and veterinary medicines that combine … (leggi tutto)
Update on treatments and vaccines against COVID-19 under development
March 31, 2020 – Supporting the rapid development and approval of effective and safe treatments for and vaccines against COVID-19 is EMA’s top priority to help save lives during the pandemic. Over recent weeks and months, the Agency has engaged with many developers of therapeutic medicines and there are a number of developments underway. However, at this point, on the basis of the preliminary data presented to the Agency, no medicine has … (leggi tutto)
Darolutamide Approved in Europe for Nonmetastatic CRPC
March 30, 2020 – The European Commission has approved darolutamide for the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC) who are at high risk for developing metastatic disease. The approval is based on results from the phase III ARAMIS trial, in which darolutamide plus androgen deprivation therapy (ADT) significantly improved metastasis-free survival (MFS) compared with placebo plus ADT (HR, 0.41 … (leggi tutto)
EMA to issue electronic certificates for medicines
March 30, 2020 – EMA has implemented a new system to issue electronic certificates for human and veterinary medicines. As of today, the Agency will no longer provide printed certificates but only electronically signed and authenticated certificates to maintain EMA’s ability to provide these documents during the COVID-19 pandemic. EMA issues certificates on behalf of the European Commission to confirm the marketing authorisation status of products either …(leggi tutto)
Dall’FDA
KTE-X19 Pivotal MCL Data Published in NEJM as FDA Weighs Approval
April 4, 2020 – Findings from the pivotal phase II ZUMA-2 trial of KTE-X19 as a treatment for adult patients with relapsed/refractory mantle cell lymphoma (MCL) were published in the New England Journal of Medicine, as the FDA considers a biologics license application (BLA) for the CAR T-cell therapy for an approval in this setting. The published results, on which the BLA were based, showed that a single infusion of KTE-X19 elicited a … (leggi tutto)
FDA Approval Sought for Naxitamab in Neuroblastoma
April 4, 2020 – Y-mAbs Therapeutics, Inc., has completed submission of a Biologics License Application (BLA) to the FDA for naxitamab for the treatment of patients with relapsed/refractory high-risk neuroblastoma. The BLA is based on data from the pivotal phase II studies 201 and 12-230. The complete data comprising the BLA package have not yet been made public, but the company intends to share the findings later this year. “As the father of a long-term … (leggi tutto)
FDA Approves Luspatercept for MDS-Associated Anemia
April 3, 2020 – The FDA has approved luspatercept-aamt for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell (RBC) units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndromes with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T). Luspatercept is not indicated for use as … (leggi tutto)
FDA Grants Remestemcel-L Priority Review for Pediatric GVHD
April 1, 2020 – The FDA has granted remestemcel-L a priority review designation for the treatment of children with steroid-refractory acute graft versus host disease (SR-aGVHD), according to Mesoblast Limited, the manufacturer of the allogeneic cell therapy. Under the Prescription Drug User Fee Act, the FDA is scheduled to decide on the application by September 30, 2020. “There is a critical need to improve survival outcomes in children suffering from the more … (leggi tutto)
FDA Grants ME-401 Fast Track Designation for Follicular Lymphoma
March 31, 2020 – The FDA has granted ME-401 Fast Track Designation for the treatment of adult patients with relapsed or refractory follicular lymphoma who have received at least 2 prior systemic therapies, according to MEI Pharma, Inc., the company developing the oral PI3K delta inhibitor. In October 2019, MEI shared the latest data from a phase Ib trial showing that ME-401 induced an overall response rate (ORR) of 78% in patients with relapsed/refractory … (leggi tutto)
FDA Approval Sought for Tivozanib in Relapsed/Refractory Renal Cell Carcinoma
March 31, 2020 – A new drug application (NDA) has been submitted to the FDA for tivozanib for the treatment of patients with relapsed/refractory renal cell carcinoma (RCC), according to Aveo Oncology, the company developing the VEGFR TKI. The NDA is based on data from the phase III TIVO-3 trial, in which the median overall survival (OS) was 16.4 months (95% CI, 13.4-22.2) for tivozanib and 19.7 months (95% CI, 15.0-24.2) for sorafenib (HR, 0.99; 95% CI … (leggi tutto)
FDA Approval Sought for Idecabtagene Vicleucel in Multiple Myeloma
March 31, 2020 – A biologics license application (BLA) has been submitted to the FDA for idecabtagene vicleucel (ide-cel; bb2121) for the treatment of adult patients with multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, according to Bristol Myers Squibb and bluebird bio, Inc., the co-developers of the BCMA-directed CAR T-cell immunotherapy. The BLA … (leggi tutto)
FDA Approves Durvalumab for Frontline Small Cell Lung Cancer
March 30, 2020 – The FDA has approved durvalumab for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) for use in combination with standard-of-care chemotherapy, including etoposide plus either carboplatin or cisplatin. The approval is based on findings from phase III CASPIAN trial, in which adding the PD-L1 inhibitor to chemotherapy reduced the risk of death by 27% compared with chemotherapy alone … (leggi tutto)
Dall’ASCO
Harvard Medical Student’s Innovation: Disinfection You Can See
April 4, 2020 – In 2014, three undergrads at Columbia University had a crazy idea for a hackathon challenge: colorize bleach so health-care workers could spot missed areas on the surfaces and personal protective equipment they are trying to disinfect. Five years later, the result is a product called Highlight®, along with $6 million in venture capital funding, pilot studies at major medical centers, data showing efficacy and high satisfaction among health- … (leggi tutto)
Oncologists on the Front Lines of the COVID-19 Pandemic: A Conversation With Miriam A. Knoll, MD
April 2, 2020 – During the coronavirus disease 2019 (COVID-19) pandemic, The ASCO Post will be interviewing oncologists on how they and their centers are dealing with the crisis. Here, we speak with Miriam A. Knoll, MD, a radiation oncologist at the John Theurer Cancer Center, Hackensack University Medical Center, New Jersey. Dr. Knoll is a contributor to Forbes, HuffPost, KevinMD.com, and blogs at ASCO Connection, writing about women in medicine … (leggi tutto)
Maintaining Blood Donations During the COVID-19 Pandemic
April 1, 2020 – A major casualty of the coronavirus disease 2019 (COVID-19) pandemic is the dramatic decrease in the number of blood donations across the United States. As more people are urged to shelter-in-place and avoid social contact, the number of cancellations in blood drives has been dramatic. According to the American Red Cross, which supplies about 40% of the nation’s blood supply, as of March 25, about 7,000 blood drives have been cancelled … (leggi tutto)
Gynecologic Cancer Screening After a Natural Disaster
April 1, 2020 – Cervical cancer screening rates were significantly affected in the years following the Great East Japan Earthquake of 2011, according to a report published by Miki et al in PLOS ONE. “Conflicts and disasters, and the social isolation that often follows, have a major impact on health care and lead to delays in the diagnosis and treatment of cancers,” said first author Yasuhiro Miki, DVM, PhD, who specializes in disaster obstetrics and gynecology … (leggi tutto)
31 marzo 2020 – Comunicazione AIFA sull’utilizzo di Clorochina e Idrossiclorochina nella terapia dei pazienti affetti da COVID-19 – Informazioni di sicurezza
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