Abstract 299P
Background
Approximately 15% of patients (pts) with intrahepatic cholangiocarcinoma (iCCA) have isocitrate dehydrogenase 1 mutations (mIDH1). Real-world clinical outcomes and treatment patterns of pts with mIDH1 and wild-type (WT) iCCA during first-line (1L) and second-line (2L) therapy remain poorly understood.
Methods
Pts with advanced or metastatic iCCA who underwent successful testing for a mIDH1 and initiated 2L treatment between 1st July 2019 and 31st December 2021 were enrolled across 17 sites in 6 countries, in this 1:1 matched case control study. Pts who received an IDH1 inhibitor at any line of treatment were excluded. Availability of data to calculate median progression-free survival (mPFS) and overall survival (mOS) were required for inclusion. Treatment type, response to treatment and safety outcomes were collected from pts medical records. PFS and OS were analyzed using the Kaplan-Meier method. Deceased pts were eligible for enrolment.
Results
A total of 64 pts (n=32 WT and n=32 mIDH1) were enrolled. The most common systemic therapy received was gemcitabine + platinum compound in the 1L (84.4%) and FOLFOX in the 2L (42.9%). mPFS and mOS of WT and mIDH1 pts overall and of those receiving FOLFOX in the 2L are shown in the table. Partial response was achieved in 31.3% of WT and 20.8% of mIDH1 pts in the 1L and in 15.4% of WT and 10.0% of mIDH1 pts in the 2L. A total of 17 and 19 pts had ≥1 treatment-related adverse event (AE) in the 1L and 2L, respectively. Treatment interruptions in the 2L were more frequent in the WT group than the mIDH1 group (50.0% vs 22.6%, respectively), with most treatment interruptions due to AEs in both groups (60.0% vs 57.1%). Table: 299P
mPFS and mOS of WT and mIDH1 pts overall and of those receiving FOLFOX in the 2L
| WT patients | mIDH1 patients | |||
| All (N=31) ∗ | FOLFOX in 2L (N=14) | All (N=31) ∗ | FOLFOX in 2L (N=14) | |
| mPFS 1L (95% CI), months | 6.3 (4.2, 9.2) | 5.0 (2.4, 9.2) | 9.6 (7.3, 13.0) | 9.4 (3.9, 17.0) |
| mPFS 2L (95% CI), months | 3.3 (2.3, 4.9) | 2.7 (1.9, 7.2) | 3.5 (2.4, 5.0) | 2.9 (1.4, 3.9) |
| mOS 2L (95% CI), months | 8.5 (6.5, 11.3) | 6.3 (3.4, 8.9) | 9.7 (5.5, 11.2) | 8.0 (3.0, 10.5) |
∗Data unavailable for N=1 in both groups. 2L, second-line. CI, confidence interval. mIDH1, mutant IDH. mOS, median overall survival. mPFS, median progression-free survival. WT, wild-type.
Conclusions
These real-world data highlight the poor prognosis of iCCA patients regardless their mutational status before arrival of targeted therapies. mOS was longer than expected for both groups, potentially due to biased selection of pts eligible for 2L therapy and a very limited number of pts.
Editorial acknowledgement
Editorial assistance was provided by Nicola Lander of Empowering Strategic Performance Ltd and supported by Servier.
Legal entity responsible for the study
Servier Affaires Médicales.
Funding
Servier Affaires Médicales.
Disclosure
D. Melisi: Financial Interests, Personal, Advisory Board: Servier, Incyte, Tahio, iOnctura, Eli Lilly, Shire, Baxter, Terumo; Financial Interests, Institutional, Research Grant: Shire, Celgene, Incyte, iOnctura, Roche. A. Lamarca: Financial Interests, Personal, Sponsor/Funding: Ipsen, Pfizer, Bayer, AAA, Sirtex, Novartis, Mylan, Delcath Advanza Pharma; Financial Interests, Personal, Invited Speaker: Merck, Pfizer, Ipsen, Incyte, AAA, QED, Servier, AstraZeneca, Eisai, Roche, Advanz Pharma; Financial Interests, Personal, Advisory Role: Eisai, Nutrica, Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, Taiho; Financial Interests, Institutional, Funding: QED, Merck, Boehringer Ingelheim, Servier, AstraZeneca, GenFit, Albireo Pharma; Non-Financial Interests, Personal, Member, Funded by Ipsen: Knowledge Network; Financial Interests, Personal, Member, Funded by Ipsen: NETConnect Initiatives. J.F. Blanc: Financial Interests, Personal, Other, Consultancy: Servier, Incyte, Tahio, Bayer, Roche, AstraZeneca, MSD. L. Perkhofer: Financial Interests, Personal, Other, Consultancy: Servier, AstraZeneca. H. Gharbi: Financial Interests, Personal, Full or part-time Employment: Servier. R. Robert: Financial Interests, Personal, Full or part-time Employment: Servier. V. Sahai: Financial Interests, Institutional, Research Grant: Acutate Therapeutics, Agios, Boehringer Ingram, Bristol Myers Squibb, Celgene, Clovis, Cornerstone, Exelixis, FibroGen, Ipsen, MedImmune, NCI, PanCAN, Relay, Repare, Syros, TransThera; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Autem, Cornerstone, Delcath Systems, GSK, Helsinn, Histosonics, Ipsen, Incyte, Kinnate, Lynx Group/Amplity, Servier, Taiho; Financial Interests, Personal, Other, Provision of equipment/supplies: BeiGene, Cornerstone; Financial Interests, Personal, Other, Travel/lodging: ASCO, Cholangiocarcinoma Foundation, Histosonics, Lynx Group/Amplity.