Effect of FGFR2 Alterations on Overall and Progression-Free Survival in Patients Receiving Systemic Therapy for Intrahepatic Cholangiocarcinoma.

Background: First-line standard-of-care therapy for advanced cholangiocarcinoma is gemcitabine plus cisplatin; there is no established second-line systemic therapy. Fibroblast growth factor receptor (FGFR)-2 fusions/rearrangements can be oncogenic drivers, occurring almost exclusively in intrahepatic cholangiocarcinoma, but little is known about whether FGFR2 status affects the response to systemic chemotherapy.

Objective: We aimed to evaluate the effects of FGFR2 status on survival outcomes in patients receiving systemic therapy for intrahepatic cholangiocarcinoma.

Truncated FGFR2 is a clinically actionable oncogene in multiple cancers.

Somatic hotspot mutations and structural amplifications and fusions that affect fibroblast growth factor receptor 2 (encoded by FGFR2) occur in multiple types of cancer. However, clinical responses to FGFR inhibitors have remained variable, emphasizing the need to better understand which FGFR2 alterations are oncogenic and therapeutically targetable. Here we apply transposon-based screening and tumour modelling in mice, and find that the truncation of exon 18 (E18) of Fgfr2 is a potent driver mutation.

Progression-Free Survival in Patients With Cholangiocarcinoma With or Without Alterations: A FIGHT-202 Post Hoc Analysis of Prior Systemic Therapy Response.

Purpose: Oncogenic fibroblast growth factor receptor (FGFR) gene alterations have been described in patients with cholangiocarcinoma (CCA). This post hoc analysis assessed progression-free survival (PFS) in patients who had received first- or second-line systemic therapy for advanced/metastatic CCA before enrollment in the phase II FIGHT-202 study (ClinicalTrials.gov identifier: NCT02924376).

Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling.

Cholangiocarcinoma (CCA) is a heterogeneous biliary tract cancer with a poor prognosis. Approximately 30% to 50% of patients harbor actionable alterations, including FGFR2 rearrangements. Pemigatinib, a potent, selective fibroblast growth factor receptor (FGFR) FGFR1-3 inhibitor, is approved for previously treated, unresectable, locally advanced or metastatic CCA harboring FGFR2 fusions/rearrangements, as detected by a US Food and Drug Administration-approved test.

Clinicogenomic Analysis of -Rearranged Cholangiocarcinoma Identifies Correlates of Response and Mechanisms of Resistance to Pemigatinib.

Pemigatinib, a selective FGFR1-3 inhibitor, has demonstrated antitumor activity in FIGHT-202, a phase II study in patients with cholangiocarcinoma harboring fusions/rearrangements, and has gained regulatory approval in the United States. Eligibility for FIGHT-202 was assessed using genomic profiling; here, these data were utilized to characterize the genomic landscape of cholangiocarcinoma and to uncover unique molecular features of patients harboring rearrangements. The results highlight the high percentage of patients with cholangiocarcinoma harboring potentially actionable genomic alterations and the diversity in gene partners that rearrange with .

FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with rearrangements.

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1-3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with rearrangements (NCT03656536).

Comparative study on the use of three different near infrared spectroscopy recording methodologies for varietal discrimination of walnuts.

Walnut fruit (Juglans regia L.) is an internationally well-known product with an important tradition of consumption. Its health benefits and economic importance in the food industry make this nut an interesting research topic.

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation.

Aim: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy.

Methods: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk.

Outcome of patients treated with palliative weekly paclitaxel plus cetuximab in recurrent head and neck cancer after failure of platinum-based therapy.

Few therapeutic options are available for recurrent/metastatic head and neck cancer when progression occurs after initial chemotherapy. We analyzed retrospectively the efficacy of weekly Paclitaxel plus Cetuximab as second line of palliative chemotherapy. Patients with squamous carcinoma of head and neck with documented progression after initial treatment were enrolled.

Anti-vascular endothelial growth factor therapy in the era of personalized medicine.

Purpose: To review the role of anti-vascular endothelial growth factor (anti-VEGF) therapies in the personalized medicine era.

Methods: We searched PubMed for prospective clinical trials published through October 2012 of anti-VEGF agents approved by the U.S.