Tibsovo (ivosidenib)

Chemoimmunotherapy is the reference first-line regimen for biomarker-unselected advanced cholangiocarcinoma. Early comprehensive genomic profiling is essential to enable timely, matched targeted therapy and maximize population-level benefit.

Treatment was well tolerated and associated with durable radiographic response with tumor reduction, partial metabolic response on FDG-PET imaging, and clinically significant improvement in neurological symptoms and quality of life. This case highlights the value of molecular tumor board-guided interpretation of genomic alterations and illustrates the potential role of IDH-targeted therapy in select patients with recurrent chordoma.

This selected real-world cohort demonstrates durable responses exceeding published benchmarks and has one of the longest follow-up periods reported for IDHi in AML. A subset of older adults with IDH-mutated AML can achieve highly durable remissions on IDHi without significant toxicity.

Performing molecular testing (in the absence of adequate tumor tissue with liquid biopsy) as early as possible is already an integral part of the treatment pathway planning for CCA patients. Early molecular testing may therefore lead to the possibility of administering targeted therapy in the first-line setting within this patient group, pending the outcomes of clinical trials.

P1, N=291, Recruiting, Institut de Recherches Internationales Servier | Trial completion date: Mar 2026 --> Dec 2026 | Trial primary completion date: Mar 2026 --> Dec 2026

P2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P1, N=2, Terminated, Northwestern University | Active, not recruiting --> Terminated; Low accrual

P2, N=3, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: May 2026 --> May 2027

P2, N=20, Recruiting, Ruijin Hospital

We identify recurrent, low-VAF IDH1/2 mutations in angiosarcoma and provide evidence that these subclonal mutations promote tumorigenesis through non-cell-autonomous mechanisms. Vascular tumors driven by subclonal IDH1 mutations responded dramatically to ivosidenib, thus revealing a novel treatment for a subset of vascular tumors.

These preliminary data might indicate that targeted therapies should be introduced in first line with different strategies depending on molecular alterations, with access to platinum-based palliative systemic anti-cancer treatment being important for patients with IDH1-mutated BTC.

Genomic profiling reveals targetable alterations-IDH1/2 mutations, FGFR2 fusions, HER2 aberrations, BRAF V600E-driving the clinical success of specific inhibitors (ivosidenib, FGFR inhibitors, HER2-targeted ADCs/antibodies, dabrafenib/trametinib). However, overcoming tumor heterogeneity, resistance mechanisms, and optimizing combination strategies remain critical challenges. This paradigm shift towards molecularly guided therapies offers significant hope for improving BTC patient survival.