Cabozantinib (CABO) tolerance and efficacy for patients with advanced hepatocellular carcinoma (HCC) after failure of sorafenib (SOR) in a French population: CLERANCE, a phase 4 trial
- Type de publi. : Article dans une revue
- Date de publi. : 01/02/2023
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Auteurs :
Philippe MerleMohamed BouattourJean-Frédéric BlancJean-Marie PeronMarilyne Debette-GratienPierre NahonEric Nguyen-KhacJean Marc PhelipEric AssenatVincent BourgeoisCarine RichouAlexandra HeurgueJean-Pierre BronowickiIsabelle Ollivier-HourmandThomas UguenStéphane CattanSylvie ThevenonCamille BouchenyPierre Pradat
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Organismes :
Hôpital de la Croix-Rousse [CHU - HCL]
Hôpital Beaujon [AP-HP]
Centre Hospitalier Universitaire de Bordeaux
Centre Hospitalier Universitaire de Toulouse
Fédération Hospitalo-Universitaire « SUrvival oPtimization in ORgan Transplantation »
AP-HP - Hôpitaux Universitaires Paris Seine-Saint-Denis
Hôpital Avicenne [AP-HP]
Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 UPJV
Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
Institut de Génétique Moléculaire de Montpellier
Hôpital Saint Eloi [CHU Montpellier]
Centre Hospitalier Boulogne-sur-mer
Service d'Hépatologie [CHRU Besançon]
Hôpital universitaire Robert Debré [Reims]
Nutrition-Génétique et Exposition aux Risques Environnementaux
Service d'Hépato-gastro-entérologie [CHRU Nancy]
CHU Caen Normandie – Centre Hospitalier Universitaire de Caen Normandie
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Centre Hospitalier Régional Universitaire [CHU Lille]
Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille]
Hôpital de la Croix-Rousse [CHU - HCL]
Hôpital de la Croix-Rousse [CHU - HCL]
Hôpital de la Croix-Rousse [CHU - HCL]
- Publié dans Journal of Clinical Oncology le 01/11/2020
Résumé : Background: CABO is approved in second (2L) or third line (3L) systemic therapy for pts with advanced HCC after SOR failure, based on results of the CELESTIAL phase 3. CLERANCE was designed to evaluate safety and efficacy of CABO in pts with HCC in real-world practice in a French population. Methods: This prospective, French multicentre (n=17), interventional study aims to recruit 110 pts with unresectable HCC when a decision of CABO treatment was made in 2L or 3L after prior sorafenib (SOR) failure, according to the French health authority approved label. The primary endpoint is the incidence of treatment-related adverse events (TRAE) of grade > 2 (NCI-CTCAE v5) by a central review committee. Secondary endpoints include overall survival (OS), objective response rate (ORR) (RECIST v1.1 per investigator assessed), progression-free survival (PFS), time to progression (TTP) and profiles of CABO administration. Results: Of 110 pts enrolled, the final analysis focused on the 99 pts who starting CABO (11 pts withdrawn due to screen failure) and followed up to 12 mo (data cut-off: November 8, 2021). Pts were mainly males (89%), 69 years median age (range 24-85), Child-Pugh A (94.9%) / B7 (5.1%), and ALBI score-1 (33%), 2 (60%), 3 (5%), not evaluated (NE) (2%). About 59% pts received CABO in 2L after SOR, whereas 41% were in 3L after SOR and another line (TKI or IO). SOR was discontinued due to tumor progression (68%) or intolerance (32%) with a median duration of 4.2 mo (95% CI 3.5-4.8) and a median dose of 800 mg (95% CI 631-800). In the 99 pts starting CABO, 128 treatment-emergent adverse events (TEAE) of grade > 2 were reported, 40 of them classified as TRAE: hand foot skin reaction (14%), diarrhea (11%), asthenia and/or anorexia and/or weight loss (12%), arterial hypertension (4%). The ORR was 7% with 58% of disease control rate (DCR). Median PFS was 6.2 mo (95% CI, 5.3-8.7), TTP 8.2 mo (95% CI 6.1-12.8), without any difference when CABO used in 2L or 3L line (with prior IO [11%] or not). OS was 11.5 mo (95% CI 9.2-14.6) since start of CABO and 23 mo (95% CI 17.3-29.4) since the first systemic line. ALBI score at 1 was an independent marker of better OS in multivariate analysis (Exp[b] 3.26, 95% CI 1.86-5.69, p<0.0001). The median duration of CABO was 5.2 mo (95% CI 3.5-6.0), the median daily dose 40 mg (95% CI 32.3-43.6), 66% of pts needed dose reduction, and permanent CABO discontinuation in 75.8% pts, due to: i) death (7%), tumor progression (54%) (median time to progression 5.3 mo; 95% CI 3.7-12.8), or AE (15.2%) (median time to AE 2.6 mo; 95% CI 1.5-7.7). Conclusions: In this final analysis of CLERANCE, most pts could start CABO (90%) 2L or 3L among the 110 enrolled pts. In real-life setting in CLERANCE, tolerability and efficacy were similar to those observed in CELESTIAL. The baseline ALBI score at 1 was strongly and independently associated with a better outcome. Clinical trial information: NCT03963206 .
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