Long-term benefit of ivosidenib in IDH1-mutated cholangiocarcinoma

In this video, Prof Dr Arndt Vogel discusses updated results from the phase IIIb ProvIDHe study, presented at ESMO GI 2026.¹ ProvIDHe is an international, single-arm phase IIIB study evaluating the safety and efficacy of ivosidenib in patients with locally advanced or metastatic IDH1-mutated cholangiocarcinoma who had received at least one prior line of systemic therapy. The study was initiated to further consolidate real-world safety and efficacy data following the phase III ClarIDHy trial, which had previously demonstrated clinical benefit with ivosidenib in this population. 

As of the data cut-off, 298 patients from 15 countries were included in the full analysis set. Median progression-free survival was 5.6 months and median overall survival was 16.4 months, reinforcing the efficacy signal seen in ClarIDHy. Prof Dr Vogel emphasises that the data are reassuring, as they confirm the activity of ivosidenib in a broader clinical-practice setting. 

A key focus of the analysis was the subgroup of long responders, defined as patients treated with ivosidenib for at least 12 months. This group represented 53 of 298 patients, or approximately one in six patients. In these long responders, median progression-free survival was 19.6 months and median overall survival had not yet been reached. Disease control was achieved in all long responders, suggesting that a clinically relevant subgroup of patients can derive prolonged benefit from treatment. 

No clear clinical or biochemical marker has yet been identified to predict which patients will become long responders. Prof Dr Vogel notes that further work is needed to better characterise this subgroup and to optimise future use of IDH1-directed therapy. Ongoing research is evaluating ivosidenib in combination strategies and in earlier lines of treatment, with the aim of increasing the proportion of patients who achieve durable benefit.