Clinical Outcomes After Progression on First-Line Therapies in IDH1 Mutated Versus Wild-Type Intrahepatic Cholangiocarcinoma Patients.

Autor: Rimini M; IRCCS San Raffaele Scientific Institute Hospital, Department of Oncology, Vita-Salute San Raffaele University, Milan, Italy. margherita.rimini@gmail.com., Fabregat-Franco C; Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital & Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Persano M; Medical Oncology, University and University Hospital, Cagliari, Italy., Burgio V; IRCCS San Raffaele Scientific Institute Hospital, Department of Oncology, Vita-Salute San Raffaele University, Milan, Italy., Bergamo F; Oncology Unit 1, Veneto Institute of Oncology - IRCCS, Padua, Italy., Niger M; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Scartozzi M; Medical Oncology, University and University Hospital, Cagliari, Italy., Rapposelli IG; Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', 47014, Meldola, Italy., Aprile G; Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy., Ratti F; Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy., Pedica F; Department of Experimental Oncology, Pathology Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy., Verdaguer H; Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital & Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Rizzato M; Oncology Unit 1, Veneto Institute of Oncology - IRCCS, Padua, Italy., Nichetti F; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Lai E; Medical Oncology, University and University Hospital, Cagliari, Italy., Cappetta A; Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy., Macarulla T; Gastrointestinal Cancer Unit, Vall d'Hebron University Hospital & Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Fassan M; Oncology Unit 1, Veneto Institute of Oncology - IRCCS, Padua, Italy., De Braud F; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Pretta A; Medical Oncology, University and University Hospital, Cagliari, Italy., Simionato F; Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy., De Cobelli F; School of Medicine, Vita-Salute San Raffaele University, 20132, Milan, Italy., Aldrighetti L; Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy., Fornaro L; Medical oncology, University Hospital of Pisa, Pisa, Italy., Cascinu S; School of Medicine, Vita-Salute San Raffaele University, 20132, Milan, Italy., Casadei-Gardini A; School of Medicine, Vita-Salute San Raffaele University, 20132, Milan, Italy.
Jazyk: angličtina
Zdroj: Targeted oncology [Target Oncol] 2023 Jan; Vol. 18 (1), pp. 139-145. Date of Electronic Publication: 2023 Jan 23.
DOI: 10.1007/s11523-022-00933-7
Abstrakt: Background: Isocitrate dehydrogenase-1 (IDH1) mutations occur in a significant proportion of intrahepatic cholangiocarcinomas (iCCAs). No data are available regarding the prognostic impact of IDH1 mutations in advanced iCCA patients after progression on first-line therapies.
Objective: We investigated the role of IDH1 mutation in advanced iCCA after progression on first-line therapies.
Patients and Methods: After progression on first-line therapies for advanced iCCA, consecutive patients were retrospectively collected. The IDH1 status was tested at baseline. This analysis aimed to examine the association between the presence of IDH1 missense mutations and survival outcomes in patients with advanced iCCA treated with a second-line therapy.
Results: The analysis included 119 patients; 56/119 (47%) were IDH1 mutated (IDH1m) and 63/119 (53%) were IDH1 wild type (IDH1 WT). At univariate analysis for overall survival (OS), the presence of IDH1 mutation was associated with a worse median OS (mOS; 8.2 vs. 14.1 months; hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.2-3.0, p = 0.0047). Patients harboring IDH1 mutations showed a worse objective response rate (ORR) compared with patients without IDH1 mutation, whereas no significant differences in disease control rate (DCR) were found. Multivariate analysis confirmed IDH1 mutations as an independent negative prognostic factor for OS (HR 1.7, 95% CI 1.1-2.7, p = 0.0256). By evaluating only patients receiving FOLFOX as second-line therapy, no statistically significant differences were found in terms of both OS and PFS between IDH1m and IDH1 WT patients. In this subset of patients, those harboring an IDH1 mutation showed a worse ORR and DCR compared with those without. Finally, at univariate analysis for OS from third-line treatment, the presence of an IDH1 mutation was associated with a trend toward a worse mOS (6.0 vs. 11.9 months; HR 1.6, 95% CI 0.8-3.2, p = 0.25).
Conclusion: The present analysis constitutes the first evidence of a negative prognostic impact of IDH1 mutations in a cohort of patients treated after progression on first-line therapies in contrast to IDH1 inhibitors.
(© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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