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

被引：5

作者：

Rimini, Margherita ^{[1
]}

Fabregat-Franco, Carles ^{[2
]}

Persano, Mara ^{[3
]}

Burgio, Valentina ^{[1
]}

Bergamo, Francesca ^{[4
]}

Niger, Monica ^{[5
]}

Scartozzi, Mario ^{[3
]}

Rapposelli, Ilario Giovanni ^{[6
]}

Aprile, Giuseppe ^{[7
]}

Ratti, Francesca ^{[8
]}

Pedica, Federica ^{[9
]}

Verdaguer, Helena ^{[2
]}

Rizzato, Mario ^{[4
]}

Nichetti, Federico ^{[5
]}

Lai, Eleonora ^{[3
]}

Cappetta, Alessandro ^{[7
]}

Macarulla, Teresa ^{[2
]}

Fassan, Matteo ^{[4
]}

De Braud, Filippo ^{[5
]}

Pretta, Andrea ^{[3
]}

Simionato, Francesca ^{[7
]}

De Cobelli, Francesco ^{[10
]}

Aldrighetti, Luca ^{[8
]}

Fornaro, Lorenzo ^{[11
]}

Cascinu, Stefano ^{[10
]}

Casadei-Gardini, Andrea ^{[10
]}

机构：

[1] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst Hosp, Dept Oncol, Milan, Italy

[2] Vall d Hebron Univ Hosp, Vall dHebron Inst Oncol VHIO, Gastrointestinal Canc Unit, Barcelona, Spain

[3] Univ & Univ Hosp Cagliari, Med Oncol, Cagliari, Italy

[4] Veneto Inst Oncol, Oncol Unit 1, IRCCS, Padua, Italy

[5] Fdn IRCCS Ist Nazl Tumori Milano, Med Oncol Dept, Milan, Italy

[6] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amado, Dept Med Oncol, I-47014 Meldola, Italy

[7] San Bortolo Gen Hosp, Azienda ULSS8 Ber, Dept Oncol, Vicenza, Italy

[8] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Liver Ctr, Hepatobiliary Surg Div, I-20132 Milan, Italy

[9] IRCCS San Raffaele Sci Inst, Dept Expt Oncol, Pathol Unit, I-20132 Milan, Italy

[10] Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy

[11] Univ Hosp Pisa, Med oncol, Pisa, Italy

来源：

TARGETED ONCOLOGY | 2023年 / 18卷 / 01期

关键词：

ISOCITRATE DEHYDROGENASE 1; MUTATIONS; CHEMOTHERAPY;

D O I：

10.1007/s11523-022-00933-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BackgroundIsocitrate 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.ObjectiveWe investigated the role of IDH1 mutation in advanced iCCA after progression on first-line therapies.Patients and MethodsAfter 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.ResultsThe 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).ConclusionThe 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.

引用

页码：139 / 145

页数：7

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