FGFR2 fusion

This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving.

This case demonstrates the significant therapeutic potential of pemigatinib in a patient with metastatic cholangiocarcinoma with FGFR2 fusion, where complete disease remission was achieved after previous progression on standard treatment.

Clinical activity of FGFRi was heterogenous across FGFR alteration and tumor types. FGFR fusions and mutations were associated with greater benefit, whereas amplifications were not. Further investigation of resistance mechanisms and development of next-generation FGFRi are needed.

Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors.

This study confirms that, despite its name, PLNTY is not limited to pediatric patients. Findings underscore the highly epileptogenic nature of PLNTY and its recognizable electroclinical features, potentially related to its distinctive neuropathology. Most PLNTYs show mitogen-activated protein kinase (MAPK) pathway activating alterations, demonstrated by BRAFV600E mutation and FGFR3 fusion.

In this retrospective analysis, ctDNA represents a practical alternative to tumor tissue for NGS-based biomarker testing in aBTC, offering improved access and faster results.

P=N/A, N=0, Temporarily Not Available, Providence Health & Services

Most patients followed an aggressive clinical course, including metastases and disease-related mortality. These findings expand the spectrum of sarcomas driven by FGFR gene fusions, underscoring the importance of molecular testing for accurate diagnosis and potential targeted therapy in high-grade sarcomas with myogenic features.

TP53 mutations were associated with poor prognosis and may predict greater benefit from ICI, supporting biomarker-driven stratification.

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.

Despite additive anti-tumor activity for FGFR and MEK inhibition in KRASmt NSCLC lines, the trial was stopped after dose escalation, as no RP2D was identified for futibatinib/binimetinib due to reversible retinopathies. Trial register number. NCT04965818. Trial registration date. 20-September-2021.

In patients with cholangiocarcinoma previously treated with immune checkpoint inhibitors (n = 20), the combination regimen achieved an ORR of 20.0% and a disease control rate of 75.0%. These findings support further development of tinengotinib, both as monotherapy and in combination with immunotherapy.