Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial
| العنوان: | Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial |
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| المؤلفون: | Valérie Vilgrain, Helena Pereira, Eric Assenat, Boris Guiu, Alina Diana Ilonca, Georges-Philippe Pageaux, Annie Sibert, Mohamed Bouattour, Rachida Lebtahi, Wassim Allaham, Hélène Barraud, Valérie Laurent, Elodie Mathias, Jean-Pierre Bronowicki, Jean-Pierre Tasu, Rémy Perdrisot, Christine Silvain, René Gerolami, Olivier Mundler, Jean-Francois Seitz, Vincent Vidal, Christophe Aubé, Frédéric Oberti, Olivier Couturier, Isabelle Brenot-Rossi, Jean-Luc Raoul, Anthony Sarran, Charlotte Costentin, Emmanuel Itti, Alain Luciani, René Adam, Maïté Lewin, Didier Samuel, Maxime Ronot, Aurelia Dinut, Laurent Castera, Gilles Chatellier, Elisabeth Delhom - Christol, Alina D Ilonca, Julie Lonjon, Mohamed Abdel-Rehim, Arnaud Dieudonné, Christophe Bazin, Carine Chagneau-Derrode, Patrick Borentain, Antoine Bouvier, Laurent Vervueren, Julia Chalaye, Hicham Kobeiter, Julien Edeline, Etienne Garin, Yan Rolland, Isabelle Archambeaud, Thomas Eugene, Eric Frampas, Christophe Cassinotto, Martine Guyot, Jean-Baptiste Hiriart, Bruno Lapuyade, Julien Vergniol, Philippe Bachellier, Julien Detour, Bernard Duclos, Michel Greget, Francois Habersetzer, Alessio Imperiale, Philippe Merle, Agnès Rode, Julie Morvan, Eric Nguyen-Khac, Thierry Yzet, Guillaume Baudin, Patrick Chevallier, Abakar Mahamat, Thierry Piche, Micheline Razzouk, Patrick Hillon, Romaric Loffroy, Michel Toubeau, Julie Vincent, Gabriele Barabino, Nadia Bouarioua, Muriel Cuilleron, Marie Ecochard, Nathalie Prevot-Bitot, Vincent Leroy, Julie Roux, Christian Sengel, Valérie Bourcier, Nathalie Ganne-Carrie, Olivier Seror, Sylvie Costo, Thông Dao, Jean-Pierre Pelage, Jérôme Dumortier, Francesco Giammarile, Pierre-Jean Valette, Nadia Ghazzar, Olivier Pellerin, Julien Taieb, Pierre Weinmann, Alexandra Heurgue-Berlot, Claude Marcus, Daniele Sommacale, Maria-Angéla Castilla-Lièvre, Sophie Maitre, Lysiane Marthey |
| المساهمون: | Hôpital Beaujon, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO) |
| المصدر: | Lancet Oncology Lancet Oncology, Elsevier, 2017, 18 (12), pp.1624-1636. ⟨10.1016/S1470-2045(17)30683-6⟩ |
| بيانات النشر: | HAL CCSD, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, medicine.medical_treatment, Brachytherapy, Administration, Oral, Kaplan-Meier Estimate, Liver transplantation, Gastroenterology, 0302 clinical medicine, Yttrium Radioisotopes, MESH: Carcinoma, Hepatocellular/drug therapy, education.field_of_study, Liver Neoplasms, Radiotherapy Dosage, MESH: Carcinoma, Hepatocellular/radiotherapy, Middle Aged, Sorafenib, Microspheres, MESH: Niacinamide/analogs & derivatives, 3. Good health, MESH: Liver Neoplasms/drug therapy, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, 030211 gastroenterology & hepatology, MESH: Phenylurea Compounds/administration & dosage, Liver cancer, medicine.drug, Adult, Niacinamide, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Internal medicine, medicine, Carcinoma, Humans, Neoplasm Invasiveness, education, Aged, Neoplasm Staging, Dose-Response Relationship, Drug, Performance status, business.industry, Phenylurea Compounds, medicine.disease, Survival Analysis, Surgery, MESH: Yttrium Radioisotopes/therapeutic use, Liver function, business, Follow-Up Studies |
| الوصف: | Summary Background Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 ( 90 Y) resin microspheres in patients with hepatocellular carcinoma. Methods SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90 Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442. Findings Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 [95% CI 0·94–1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [ vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related. Interpretation In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments. Funding Sirtex Medical Inc. |
| اللغة: | English |
| تدمد: | 1470-2045 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37960b5209b2b33f51aee9e80e06e797Test https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01727346Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....37960b5209b2b33f51aee9e80e06e797 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14702045 |
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