Chirurgia del Fegato a Firenze!

Dal 1° Marzo 2023, Chirurgia del Fegato sarà all'Università di Firenze
AOUC Azienda Ospedaliero-Universitaria Careggi - Largo Brambilla, 3 - 50134 Firenze

L’immunoterapia con cemiplimab prima della resezione epatica per epatocarcinoma

La rivista scientifica The Lancet Gastroenterology & Hepatology pubblica i risultati dello studio di fase di fase 2 NCT03916627 sull’uso pre-operatorio del cemiplimab (un farmaco immunoterapico anti-PD-1) in pazienti con epatocarcinoma resecabile.

Dei 20 pazienti con epatocarcinoma resecato che avevano ricevuto il farmaco prima dell’operazione, quattro (20%) hanno avuto una significativa necrosi tumorale. Tre (15%) di questi 20 pazienti hanno avuto una risposta parziale e tutti gli altri pazienti hanno mantenuto una malattia stabile.

Lo studio è il più grande che avvalora il dato a favore della monoterapia perioperatoria mirata al PD-1 nel carcinoma epatocellulare. Anche se lo studio è limitato dal piccolo numero di pazienti, ha però dimostrato l’attività clinica del cemiplimab.

I risultati sono di certo preliminari, e la piccola popolazione coinvolta potrebbe non essere responsabile di una covarianza; tuttavia, la popolazione di pazienti in questo studio è rappresentativa di quella più globale di quelli portatori del carcinoma epatocellulare e risposte all’immunoterapia simili o comparabili sono state osservate anche in sottogruppi come pazienti asiatici e non asiatici

Questo studio, insieme ad altri studi di immunoterapia neoadiuvante in molti altri tipi di tumore, supporta di continuare a valutare l’uso dell’immunoterapia perioperatoria per ridurre i tassi di recidiva e il possibile sviluppo di malattia non più resecabile o metastatica.

 

La referenza bibliografica per questo evento è:

Thomas U Marron, Maria Isabel Fiel, Pauline Hamon, Nathalie Fiaschi, Edward Kim, Stephen C Ward, Zhen Zhao, Joel Kim, Paul Kennedy, Ganesh Gunasekaran, Parissa Tabrizian, Deborah Doroshow, Meredith Legg, Ashley Hammad, Assaf Magen, Alice O Kamphorst, Muhammed Shareef, Namita T Gupta, Raquel Deering, Wei Wang, Fang Wang, Pradeep Thanigaimani, Jayakumar Mani, Leanna Troncoso, Alexandra Tabachnikova, Christie Chang, Guray Akturk, Mark Buckup, Steven Hamel, Giorgio Ioannou, Clotilde Hennequin, Hajra Jamal, Haley Brown, Antoinette Bonaccorso, Daniel Labow, Umut Sarpel, Talia Rosenbloom, Max W Sung, Baijun Kou, Siyu Li, Vladimir Jankovic, Nicola James, Sara C Hamon, Hung Kam Cheung, Jennifer S Sims, Elizabeth Miller, Nina Bhardwaj, Gavin Thurston, Israel Lowy, Sacha Gnjatic, Bachir Taouli, Myron E Schwartz, Miriam Merad: Neoadjuvant cemiplimab for resectable hepatocellular carcinoma: a single-arm, open-label, phase 2 trial. In: The Lancet Gastroenterology and Hepatology, vol. 7, no. 3, pp. 219 – 229, 2022, ISSN: 24681253, (Cited by: 7).

Abstract

Background: Surgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma. Methods: For this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing. Findings: Between Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks. Interpretation: This report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma. Funding: Regeneron Pharmaceuticals © 2022 Elsevier Ltd

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