IDH1 mutation + FGFR2 fusion

The responsiveness of gastrointestinal stromal tumors to imatinib requires validation via molecular testing. Patients diagnosed with pancreatic cancer may see enhanced survival rates by targeted therapy addressing microsatellite instability and BRCA mutations. In bile duct malignancies, especially intrahepatic cholangiocarcinoma of the small duct variant, the analysis of IDH1 mutations and FGFR2 fusions presents new treatment prospects.

FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%) were the most common second-line therapies... The rate of actionable molecular alterations detected via ctDNA is 18%, comparable to reports from tissue-based testing. Patients with aCCA are often tested before starting first or second LOT. Patients with ctDNA-detected IDH1 mutations treated with ivosidenib and had a trend toward improved rwTTD and rwTTNT, although it did not reach statistical significance.

They were offered less frequently first-line systemic therapy (87% vs 97%, p<0.0001)(gemcitabine 3% vs 0.3%; gemcis 31% vs 35%; gemox 54% in 2 groups; p=0.007) and molecular profiling (43% vs 65%, p<0.0001) than pts <70...If treated, PFS of older pts was similar to younger pts. Molecular profiling was less often performed in older pts.

We introduce findings from preclinical immunotherapy studies, discuss future immune-mediated treatment options, and provide a summary of results from clinical trials testing immune-based approaches in patients with cholangiocarcinoma. This Review provides a thorough survey of our knowledge on immune signatures and immunotherapy in cholangiocarcinoma.

Two lines of chemotherapy are currently recommended in France, with cisplatin-gemcitabine and 5 FU-oxaliplatin as first and second-line treatment respectively, allowing a median survival of approximately one year...To date, only ivosidenib and pemigatinib, targeting IDH1 mutations and FGFR2 fusions respectively, are approved in France for pre-treated patients with these molecular alterations. Many other potentially targetable alterations are found in BTC, including mutations in genes involved in DNA repair, BRAF, HER2 and the recently exploited KRASG12C mutation. This review will focus on targetable mutations in BTC and develop the main molecules that can be used in BTC with these actionable alterations, offering new therapeutic perspectives for these patients, with the ultimate goal of improving their prognosis.

ESCAT represents a tool to guide clinicians in fine-tuning use of molecular profiling data to choose matched targeted therapies. Our data demonstrate that targeted treatment administered per alteration actionability according to ESCAT is associated with improved survival in cholangiocarcinoma, particularly in ESCAT I-II intrahepatic cholangiocarcinoma.

Since 2010, chemotherapy with gemcitabine and cisplatin is considered the standard of care in the palliative situation. The current study landscape clearly shows that precision medicine will play an important role in the therapy of biliary malignancies and underlines the importance of early tumor genetic diagnostics. In this article we provide an overview of systemic therapy concepts in the adjuvant and palliative setting.