Oggi in Oncologia
Final results of DIADEM, a phase II study to investigate the efficacy and safety of durvalumab in advanced pretreated malignant pleural mesothelioma
Malignant pleural mesothelioma (MPM) is a cancer with a high mortality rate and few therapeutic options. After platinum-pemetrexed combination, no further promising drug seems to be effective. Immune checkpoint inhibitors may have some activity in pretreated patients and no data are available in this population about durvalumab.DIADEM was a multicenter, open-label, single-arm, phase II trial aimed at evaluating the efficacy and safety of durvalumab … (leggi tutto)
Il mesotelioma pleurico (MPM) ha tutt’oggi un alto tasso di mortalità e poche opzioni terapeutiche disponibili. Infatti, ad eccezione della combinazione di platino e pemetrexed, nessun altro regime chemioterapico si è dimostrato efficace in questa patologia, che recentemente ha visto i risultati positivi dell’immunoterapia, in particolare con la combinazione di nivolumab e ipilimumab. Recenti studi hanno inoltre evidenziato il potenziale degli ImmunoCheckpoint Inhibitors in pazienti pretrattati, ma non ci sono ancora dati disponibili sull’utilizzo del durvalumab in questo setting.
Canova S. et al hanno recentemente pubblicato su ESMO Open i risultati finali dello studio di fase II DIADEM. In particolare, tale studio open-label, singolo braccio e multicentrico ha valutato l’efficacia e la sicurezza del durvalumab in pazienti affetti da MPM localmente avanzato o metastatico andati incontro a progressione dopo chemioterapia a base di platino e pemetrexed. I pazienti hanno ricevuto durvalumab 1500 mg ogni 4 settimane per 12 mesi o fino a tossicità inaccettabile. Endpoint primario del trial era il tasso di pazienti liberi da progressione a 16 settimane (PFS16wks) calcolato dall’inizio del trattamento. Gli endpoint secondari comprendevano la sopravvivenza libera da progressione (PFS), la sopravvivenza globale (OS), il tasso di risposta obiettiva (ORR) e la sicurezza.
Un totale di 69 pazienti, con età media di 69 anni (range 44-82) sono stati arruolati nello studio, di questi 62 pazienti (89.9%) avevano un’istologia epitelioide. Come trattamento di prima linea, tutti i pazienti hanno ricevuto trattamento chemioterapico a base di platino e pemetrexed (60.9% carboplatino e 39.1% cisplatino). A marzo 2021, il follow-up mediano è stato di 9.2 mesi (range 5.2-11.1). Un totale di 6 pazienti (8.7%) hanno completato il trattamento per i 12 mesi previsti, mentre 60 pazienti hanno discontinuato il trattamento (42 per progressione di malattia e 4 per exitus). 17 pazienti (28.3%, 95%CI 17.5%-41.4%) erano liberi da progressione a 16 settimane. Eventi avversi di grado 3 e 4 si sono riscontrati in circa il 18.6 % (n=11) dei pazienti, mentre solo in un paziente (1.4%) è stato riscontrato un evento avverso di grado >3 correlato al trattamento. Si è registrato un solo decesso legato al farmaco. In conclusione, durvalumab non ha dimostrato efficacia clinica in pazienti pretrattati affetti da mesotelioma pleurico (MPM).
Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial
Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501) ... (leggi tutto)
Sunitinib è un inibitore tirosin chinasico multitarget (TKI), approvato per i pazienti affetti da Gastrointestinal Stromal Tumor (GIST) avanzato a fallimento da imatinib. Ripretinib è uno switch-control TKI approvato per GIST avanzato dopo trattamento con 3 o più linee di TKI, incluso imatinib. Bauer et al hanno recentemente pubblicato sul Journal of Clinical Oncology i dati di efficacia e sicurezza di ripretinib versus sunitinib in pazienti con GIST avanzato precedentemente trattati con imatinib. I pazienti sono stati randomizzati 1:1 a trattamento con ripretinib 150 mg o sunitinib 50 mg (4 weeks on/2weeks off) e stratificati per la mutazione KIT\PDGFRA e intolleranza ad imatinib. Endpoint primario era la sopravvivenza libera da progressione (PFS), mentre gli endpoint secondari includevano il tasso di risposta obiettiva (ORR), la sicurezza e i patient-reported outcome.
Un totale di 453 pazienti è stato arruolato a trattamento con ripretinib [intention to treat population (ITT) n=226; KIT ex.11 ITT n=163) o con sunitinib (ITT n=227, Ki ex.11 ITT n=164). La sopravvivenza libera da progressione (PFS) mediana per i pazienti in trattamento con ripretinib e sunitinib e mutazione KIT ex.11 è stata di 8.3 e 7.0 mesi, rispettivamente (HR 0.88, 95%CI 0.66-1.16, p=0.36). La PFS mediana nella popolazione ITT è risultata di 8.0 e 8.3 mesi, rispettivamente (HR 1.05, 95% CI 0.82-1.33, p=0.72). L’ORR è stata maggiore per ripretinib rispetto a sunitinib nella ITT population KIT ex.11 (23.9% vs 14.6%, p=0.03). In generale, ripretinib è stato associato a un buon profilo di sicurezza, con meno eventi avversi di grado 3-4 (41.3% vs 65.6%, p=0.0001), e migliori patient-reported outcomes.
Pertanto, ripretinib non ha mostrato superiorità in termini di sopravvivenza libera da progressione (PFS) rispetto a sunitinib, sebbene abbia avuto significativa attività clinica, a fronte di minor tasso di eventi avversi di grado 3-4, e miglior tollerabilità. Sono necessari ulteriori trial con follow-up prolungati per valutare i dati in termini di sopravvivenza globale (OS).
Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial
We evaluated the efficacy and safety of pembrolizumab in patients from Asia with previously treated advanced hepatocellular carcinoma (HCC). In a double-blind, phase III trial, 453 patients with advanced HCC and progression during or after treatment with or intolerance to sorafenib or oxaliplatin-based chemotherapy were randomly assigned in a 2:1 ratio to receive pembrolizumab (200 mg) or placebo once every 3 weeks for ≤ 35 cycles plus best supportive care ... (leggi tutto)
Qin et al hanno recentemente pubblicato sul Journal of Clinical Oncology i risultati del loro lavoro che ha valutato l’efficacia e la sicurezza di pembrolizumab in pazienti asiatici precedentemente trattati per epatocarcinoma avanzato (HCC).
In tale studio di fase III, in doppio cieco, randomizzato, sono stati arruolati 453 pazienti affetti da HCC avanzato e in progressione da trattamento con sorafenib o chemioterapia a base di oxaliplatino. Sono stati inoltre inclusi anche i pazienti risultati intolleranti al trattamento con sorafenib. I pazienti arruolati nello studio sono stati randomizzati 2:1 a ricevere pembrolizumab 200 mg dose flat o placebo ogni 3 settimane fino ad un massimo di 35 cicli più best supportive care. Endpoint primario dello studio era la sopravvivenza globale (OS), mentre gli endpoint secondari includevano la sopravvivenza libera da progressione (PFS) e il tasso di risposta obiettiva (ORR).
Dal punto di vista dei risultati, l’OS mediana è risultata prolungata nel braccio sottoposto a trattamento con pembrolizumab rispetto al placebo (14.6 vs 13.0 mesi, HR 0.79, 95%CI 0.63-0.99 p=0.018). Per quanto riguarda la PFS mediana, è stata maggiore nel gruppo con pembrolizumab rispetto al gruppo sottoposto a trattamento con placebo (2.6 vs 2.3 mesi, HR 0.74, 95%CI 0.60-0.92, p=0.0032). L’ORR è stata maggiore nel gruppo con pembrolizumab (12.7% 95%CI 9.1-17.0) rispetto al gruppo placebo (1.3%, 95%CI 0.2-4.6, p<0.0001).
Gli eventi avversi correlati al trattamento con pembrolizumab sono stati riportati nel 66.9% dei pazienti (grado 3 per il 12.0%, grado 4 per il 1.3%, mentre grado 5 per il 1.0%); d’altra parte il 49.7% dei pazienti (grado 3 per il 5.9%, e l’0% per grado 4 e 5) nel gruppo sottoposto a placebo ha riportato un evento avverso.
In conclusione, in pazienti asiatici precedentemente trattati per HCC avanzato, pembrolizumab ha dimostrato un prolungamento statisticamente significativo di OS, PFS, ed ORR rispetto al placebo.
In Europa
Sotorasib Shows Promising Activity and Acceptable Safety in Patients with Previously Treated KRAS p.G12C–Mutated Advanced Pancreatic Cancer
Jan 10, 2023 – In a phase I/II CodeBreaK 100 study, sotorasib monotherapy showed promising anticancer activity in patients with heavily pretreated KRAS p.G12C–mutated advanced pancreatic cancer. Treatment with sotorasib resulted in a response in 21% of the patients and a median progression-free survival (PFS) of 4 months. Overall, sotorasib was associated with mainly low-grade side effects in the heavily pretreated population in this study … (leggi tutto)
EMA Recommends Extension of Therapeutic Indications for Durvalumab and Adopts a Positive Opinion for Tremelimumab
Dec 23, 2022 – On 15 December 2022, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product durvalumab (Imfinzi). The marketing authorisation holder for this medicinal product is AstraZeneca AB … (leggi tutto)
EMA Recommends Extension of Therapeutic Indications for Trastuzumab Deruxtecan
Dec 22, 2022 – On 15 December 2022, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product trastuzumab deruxtecan (Enhertu). The marketing authorisation holder for this medicinal product is Daiichi Sankyo Europe GmbH .… (leggi tutto)
Mutational Patterns Drive Metastatic Aggressiveness of Appendiceal Adenocarcinomas
Dec 21, 2022 – A comprehensive molecular analysis performed in patients with appendiceal adenocarcinomas revealed distinct molecular subtypes: a clinically indolent RAS-mutated/GNAS-wild-type/TP53-wild-type subtype; a chemotherapy-resistant GNAS-mutated predominant subtype; and an aggressive, highly aneuploid TP53-mutated predominant subtype. The study findings highlight the value of performing somatic tumour profiling for this relatively rare malignancy … (leggi tutto)
Dall’FDA
FDA Grants Orphan Drug Designation to Azeliragon for GBM
Jan 10, 2023 – The FDA has granted an orphan drug designation to azeliragon (formerly TTP488) for the treatment of patients with glioblastoma (GBM) according to an announcement from Cantex Pharmaceuticals. The company licensed the drug from vTv Therapeutics Inc, which had been initially under development for Alzheimer’s disease. “Receiving FDA orphan drug status for azeliragon highlights the significant unmet need for novel treatment options for patients with GBM … (leggi tutto)
FDA Grants Fast Track Status to BT8009 for Previously Treated Locally Advanced or Metastatic Urothelial Cancer
Jan 5, 2023 – The FDA has granted a fast track designation to BT8009 for use as a monotherapy in adult patients with previously treated locally advanced or metastatic urothelial cancer, according to an announcement from Bicycle Therapeutics, plc. The investigative agent is a bicycle peptide toxin conjugate that targets Nectin-4, which is highly expressed on the surface of cancer cells in a broad range of solid tumors.2,3 The agent was developed to have high affinity binding and to be highly selective … (leggi tutto)
FDA Approval Sought for Cosibelimab in Advanced Cutaneous Squamous Cell Carcinoma
Jan 4, 2023 – A biologics license application (BLA) has been submitted to the FDA seeking the approval of cosibelimab (formerly CK-301), an investigational anti–PD-L1 antibody, for the treatment of patients with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or radiation. The application was based on positive efficacy and safety data from an ongoing, registrational phase … (leggi tutto)
FDA Grants Breakthrough Device Designation for Blood Test for Inaccessible Brain Tumors
Jan 4, 2023 – The FDA has granted breakthrough device designation for the TriNetratm-Glio blood test to help in the diagnosis of brain tumors, according to an announcement from Datar Cancer Genetics, Inc. The TriNetra-Glio liquid biopsy is intended to detect the cells released in the blood from the brain tumor, which are extremely rare and difficult to detect. TriNetra-Glio is indicated for patients with intracranial space-occupying lesions where a biopsy is unviable due to the inaccessibility … (leggi tutto)
FDA Grants Breakthrough Therapy Designation to Adagrasib Plus Cetuximab for KRAS G12C–Mutated Advanced CRC
Dec 22, 2022 – The FDA has granted a breakthrough therapy designation to adagrasib (Krazati) plus cetuximab (Erbitux) in patients with KRAS G12C–mutated, advanced colorectal cancer (CRC) whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy. he designation was supported by data from the CRC cohort of the phase 1b KRYSTAL-1 trial (NCT03785249) … (leggi tutto)
Dall’ASCO
First ASCO Guideline for Immunotherapy and Targeted Therapy in Advanced Gastroesophageal Cancer Now Available
Jan 6, 2023 – An ASCO Expert Panel has developed a guideline for immunotherapy and targeted therapy in patients with advanced gastroesophageal cancer. The recommendations underscore the importance of testing patients for multiple biomarkers—including HER2 status, levels of PD-L1, and mismatch repair status — to provide optimal care. The treatment of gastroesophageal cancer has significantly evolved over the past several years, but clinical trial participation remains …. (leggi tutto)
ASCO Endorses CAP Guideline to Better Define Who Benefits From Immune Checkpoint Inhibitor Therapy
Jan 6, 2023 – ASCO has endorsed a new guideline from the College of American Pathologists (CAP) on the use of mismatch repair (MMR) and microsatellite instability (MSI) testing, which could help oncologists more accurately identify patients who may be suitable candidates for immune checkpoint inhibitor (ICI) therapy. “Immunotherapy is approved as a tumor site–agnostic therapy based on MSI, meaning you can have a tumor form anywhere in the body, and if it demonstrates MSI …. (leggi tutto)
Targeting KRAS G12C Is a Significant Milestone in Metastatic Colorectal Cancer, But Work Remains
Jan 5, 2023 – Colorectal cancer (CRC) is the second most common cancer worldwide, and KRAS mutations exist in 40% of metastatic CRC cases; therefore, effective targeted therapies for patients with KRAS-mutated mCRC are sorely needed. Patients with KRASG12C mutations represent a small proportion of mCRC diagnoses, with KRAS inhibitors (sotorasib and adagrasib) as monotherapy and in combination with other-target inhibitors such as panitumumab and cetuximab …. (leggi tutto)
Liver Transplantation as Treatment for Liver Malignancies: A New Era Dawns in Transplant Oncology
Jan 5, 2023 – The role of liver transplantation in hepatocellular carcinoma is expanding to include patients defined by biologic rather than size and number criteria. Liver transplantation has emerged as a potential curative option for select patients with unresectable colorectal liver metastases and localized intrahepatic cholangiocarcinomas. Systemic therapies, including immune checkpoint inhibitors, are being explored in clinical trials as neoadjuvant treatment …. (leggi tutto)
What’s Driving the Rise of Colon Cancer in Young Adults?
Jan 5, 2023 – The incidence of early-onset colorectal cancer (EO-CRC) in people younger than age 50 is rising globally. Diet, microbiome composition, and germline alterations to mismatch repair genes may contribute to EO-CRC, but many cases are sporadic. Focused support for patients with EO-CRC during their therapy, as well as education for primary providers and oncologists on diagnosing and caring for these patients, are needed … (leggi tutto)
Drug Development in Hepatocellular Carcinoma: Leveraging Lessons From the Past to Build the Future
Jan 5, 2023 – The past decade has seen substantial progress in drug development in hepatocellular carcinoma (HCC), with the standard of care shifting from sorafenib to atezolizumab plus bevacizumab during an explosion of immunotherapeutic research. Mixed results in recent immunotherapy trials and discrepancies in previous clinical trial endpoints are challenging the field to determine a surrogate endpoint for survival …. (leggi tutto)
Role of Anti–CD38 Antibody Therapy in Induction and Maintenance in Newly Diagnosed Multiple Myeloma: How to Adopt in Clinical Practice
Jan 4, 2023 – The addition of CD38 antibodies improves the depth of response as measured by very good partial response and minimal residual disease rates after induction and after transplant. The ALCYONE and MAIA trials demonstrated that the addition of daratumumab to the bortezomib, melphalan, and prednisone regimen or lenalidomide and dexamethasone improves both progression-free survival … (leggi tutto)
How Telemedicine Can Transform Clinical Research and Practice
Dec 25, 2022 – The COVID-19 pandemic transformed the world, and nowhere more so than in the health-care arena. Significant changes happened almost overnight in the delivery of medical care to focus on the safety and convenience of patients, staff, and providers. Although pilot efforts to integrate telemedicine had begun prior to the pandemic, the immediacy of the response to the crisis forced our clinicians, staff, and patients to adopt … (leggi tutto)
Pillole dall’AIFA
9 gennaio 2023 – Tecartus® (brexucbtagene autoleucel). Disponibile il report tecnico scientifico
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3 gennaio 2022 – Chiusura Managed Entry Agreements (MEA) Registri ICLUSIG
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23 dicembre 2022 – Esiti della riunione del Comitato Prezzi e Rimborso (CPR)
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22 dicembre 2022 – Registro degli Studi Osservazionali (RSO – Attivazione a partire dal 31 gennaio 2023
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22 dicembre 2022 – Sperimentazioni cliniche decentrate: le Raccomandazioni del Network regolatorio europeo sui medicinali
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