Margherita Rimini1, Valentina Burgio2, Lorenzo Antonuzzo3,4, Lorenza Rimassa5,6, Ester Oneda7, Daniele Lavacchi3, Nicola Personeni6, Francesca Ratti8, Federica Pedica9, Angelo Della Corte10, Mara Persano11, Francesco De Cobelli12, Luca Aldrighetti8, Mario Scartozzi11, Stefano Cascinu12, Andrea Casadei-Gardini12. 1. Department of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy. margherita.rimini@gmail.com. 2. Department of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy. 3. Clinical Oncology Unit, Careggi University Hospital, Florence, Italy. 4. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 5. Department of Biomedical Sciences, Humanitas University, Milan, Italy. 6. Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Milan, Italy. 7. Oncology Department, Poliambulanza Hospital of Brescia, Brescia, Italy. 8. Hepatobiliary Surgery Department, IRCCS San Raffaele Hospital, Milan, Italy. 9. Department of Pathology, San Raffaele Scientific Institute, Milan, Italy. 10. Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy. 11. Oncology Department, University Hospital of Cagliari, Cagliari, Italy. 12. Vita-Salute University San Raffaele, Milan, Italy.
Abstract
BACKGROUND: The results of the phase III ClarIDHy trial have led to US FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. OBJECTIVE: In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib. PATIENTS AND METHODS: Patients treated with ivosidenib as second and third line for advanced CCA were collected with the aim of evaluating the survival outcomes. A molecular study has been performed by next-generation sequencing assay. RESULTS: After a median follow up of 9.4 months, median progression-free survival (PFS) from the start of treatment with ivosidenib was 4.4 months (95% confidence interval [CI] 3.3-5.8), whereas median overall survival (OS) was not reached. The disease control rate was 62.5%, with two patients achieving a partial response (25%); 12.5% of patients experienced a treatment-related adverse event (AE), but no grade 3 or higher AEs were reported. The observed grade 2 AEs were prolonged QT interval and hypomagnesemia (25% of the sample). Molecular profiling was performed on six of eight patients, highlighting TP53, BAP1, CDKN2A and CDKN2B as the most common co-altered genes in these patients. CONCLUSION: Efficacy outcomes were consistent with those reported in the ClarIDHy trial. Real-world experiences on larger samples are needed in order to confirm our results.
BACKGROUND: The results of the phase III ClarIDHy trial have led to US FDA approval of ivosidenib as a therapeutic option for patients with locally advanced or metastatic cholangiocarcinoma (CCA) harboring isocitrate dehydrogenase 1 (IDH1) mutations. OBJECTIVE: In this study, we report the first real-world experience including eight patients with previously treated locally advanced or metastatic IDH1-mutated CCA treated with ivosidenib. PATIENTS AND METHODS: Patients treated with ivosidenib as second and third line for advanced CCA were collected with the aim of evaluating the survival outcomes. A molecular study has been performed by next-generation sequencing assay. RESULTS: After a median follow up of 9.4 months, median progression-free survival (PFS) from the start of treatment with ivosidenib was 4.4 months (95% confidence interval [CI] 3.3-5.8), whereas median overall survival (OS) was not reached. The disease control rate was 62.5%, with two patients achieving a partial response (25%); 12.5% of patients experienced a treatment-related adverse event (AE), but no grade 3 or higher AEs were reported. The observed grade 2 AEs were prolonged QT interval and hypomagnesemia (25% of the sample). Molecular profiling was performed on six of eight patients, highlighting TP53, BAP1, CDKN2A and CDKN2B as the most common co-altered genes in these patients. CONCLUSION: Efficacy outcomes were consistent with those reported in the ClarIDHy trial. Real-world experiences on larger samples are needed in order to confirm our results.
Authors: Juan Valle; Harpreet Wasan; Daniel H Palmer; David Cunningham; Alan Anthoney; Anthony Maraveyas; Srinivasan Madhusudan; Tim Iveson; Sharon Hughes; Stephen P Pereira; Michael Roughton; John Bridgewater Journal: N Engl J Med Date: 2010-04-08 Impact factor: 91.245
Authors: Ghassan K Abou-Alfa; Teresa Macarulla; Milind M Javle; Robin K Kelley; Sam J Lubner; Jorge Adeva; James M Cleary; Daniel V Catenacci; Mitesh J Borad; John Bridgewater; William P Harris; Adrian G Murphy; Do-Youn Oh; Jonathan Whisenant; Maeve A Lowery; Lipika Goyal; Rachna T Shroff; Anthony B El-Khoueiry; Bin Fan; Bin Wu; Christina X Chamberlain; Liewen Jiang; Camelia Gliser; Shuchi S Pandya; Juan W Valle; Andrew X Zhu Journal: Lancet Oncol Date: 2020-05-13 Impact factor: 41.316
Authors: Angela Lamarca; Daniel H Palmer; Harpreet Singh Wasan; Paul J Ross; Yuk Ting Ma; Arvind Arora; Stephen Falk; Roopinder Gillmore; Jonathan Wadsley; Kinnari Patel; Alan Anthoney; Anthony Maraveyas; Tim Iveson; Justin S Waters; Claire Hobbs; Safia Barber; W David Ryder; John Ramage; Linda M Davies; John A Bridgewater; Juan W Valle Journal: Lancet Oncol Date: 2021-03-30 Impact factor: 41.316
Authors: Andrew X Zhu; Teresa Macarulla; Milind M Javle; R Kate Kelley; Sam J Lubner; Jorge Adeva; James M Cleary; Daniel V T Catenacci; Mitesh J Borad; John A Bridgewater; William P Harris; Adrian G Murphy; Do-Youn Oh; Jonathan R Whisenant; Maeve A Lowery; Lipika Goyal; Rachna T Shroff; Anthony B El-Khoueiry; Christina X Chamberlain; Elia Aguado-Fraile; Sung Choe; Bin Wu; Hua Liu; Camelia Gliser; Shuchi S Pandya; Juan W Valle; Ghassan K Abou-Alfa Journal: JAMA Oncol Date: 2021-11-01 Impact factor: 31.777