Characterization of FGFR Alterations and Activation in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer.

Purpose: The Genomic Analysis of High-Risk Non-Muscle-Invasive Bladder Cancer (GARNER) study investigated FGFR alteration (ALT) frequency and the clinical outcome relationship with Bacillus Calmette-Guérin (BCG) treatment in high-risk non-muscle-invasive bladder cancer (HR-NMIBC). An FGFR predictive response signature (FGFR-PRS) was discovered that identifies patients with an activated FGFR pathway who could potentially benefit from FGFR-targeted therapy beyond those who are FGFR ALT (+).

Experimental Design: Pretreatment tumor samples and clinical data were analyzed from 582 BCG-treated patients with HR-NMIBC.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Erdafitinib vs Enfortumab Vedotin in Patients with Locally Advanced Metastatic Urothelial Carcinoma.

For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC).

Effect of Erdafitinib on the Pharmacokinetics of Midazolam and Metformin in Patients With Advanced Solid Tumors Harboring FGFR Gene Alterations.

Erdafitinib, an oral pan-FGFR inhibitor, is used in locally advanced or metastatic urothelial carcinoma for adults with FGFR3 genetic alterations and whose disease progressed following prior systemic therapy. This drug-drug interaction substudy evaluated the effect of erdafitinib on the pharmacokinetics of midazolam (cytochrome P450 3A4 substrate), and metformin (organic cation transporter 2 substrate). Twenty-five patients with advanced solid tumors harboring FGFR gene alterations received pretreatment with single doses of midazolam and metformin, followed by a daily dose of erdafitinib.

Phase 3 THOR Japanese subgroup analysis: erdafitinib in advanced or metastatic urothelial cancer and fibroblast growth factor receptor alterations.

Background: In the THOR trial (NCT03390504) Cohort 1, erdafitinib demonstrated significantly prolonged overall survival (OS) (median 12.1 versus 7.8 months) and reduced risk of death by 36% (hazard ratio 0.

Development and deployment of a histopathology-based deep learning algorithm for patient prescreening in a clinical trial.

Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients.

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma.

Background: Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with -altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti-programmed cell death protein 1 [PD-1] or anti-programmed death ligand 1 [PD-L1] agents) are unclear.

Methods: We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible alterations who had progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1.

Erdafitinib in patients with advanced solid tumours with FGFR alterations (RAGNAR): an international, single-arm, phase 2 study.

Background: FGFR alterations are reported across various malignancies and might act as oncogenic drivers in multiple histologies. Erdafitinib is an oral, selective pan-FGFR tyrosine kinase inhibitor with activity in FGFR-altered advanced urothelial carcinoma. We aimed to evaluate the safety and activity of erdafitinib in previously treated patients with FGFR-altered advanced solid tumours.

Outcomes of Patients with Advanced Urothelial Carcinoma after Anti-programmed Death-(ligand) 1 Therapy by Fibroblast Growth Factor Receptor Gene Alteration Status: An Observational Study.

Background: Clinical outcomes of anti-programmed death‑(ligand) 1 (anti-PD-[L]1) therapy in patients with locally advanced or metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (+) remain unclear; recent studies have reported either comparable or poorer outcomes versus patients without alterations (-)

Objective: To analyze the outcomes of patients with mUC and any (mutations or fusions) who received anti-PD-(L)1 therapy.

Design Setting And Participants: In this noninterventional, retrospective, multicenter study, clinical practice data were collected from - patients who received prior immunotherapy between May 2018 and July 2019.

Outcome Measurements And Statistical Analysis: Investigator‑determined overall response rate (ORR), disease control rate (DCR), and overall survival (OS) were assessed in multivariate and unadjusted analyses.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial.

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries.

Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer.

Background: As with other alkylating agents, cardiac dysfunction can occur with trabectedin therapy for advanced soft tissue sarcomas (STS) or recurrent ovarian cancer (ROC) where treatment options for advanced disease are still limited. Cardiac safety for trabectedin monotherapy (T) for STS or in combination with pegylated liposomal doxorubicin (T+PLD) for ROC was evaluated in this retrospective postmarketing regulatory commitment.

Methods: Patient data for multiple cardiac-related treatment-emergent adverse events (cTEAEs) were evaluated in pooled analyses of ten phase 2 trials, one phase 3 trial in STS (n = 982), and two phase 3 trials in ROC (n = 1231).

Data on prior pegylated liposomal doxorubicin (PLD) treatment in recurrent ovarian cancer: Post-hoc data analysis from the phase 3 randomized, open-label study comparing trabectedin and PLD versus PLD alone in patients with recurrent ovarian cancer.

The data presented herein are supplementary to our published primary article "A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer"[1]. The exploratory analysis evaluated the impact of prior pegylated liposomal doxorubicin (PLD) therapy in patients who participated in a randomized, open-label study comparing combination therapy of trabectedin and PLD vs PLD alone in third-line recurrent ovarian cancer (ROC). These exploratory analyses showed that prior treatment with PLD in ROC does not impact the response and survival rates nor does it increase toxicities or negatively influence survival and response rates in both treatment groups.

A phase 3 randomized, open-label, multicenter trial for safety and efficacy of combined trabectedin and pegylated liposomal doxorubicin therapy for recurrent ovarian cancer.

Objective: This phase 3 study aimed to compare overall survival (OS) of women with platinum-sensitive, recurrent ovarian cancer (ROC) treated with third-line trabectedin (T) + pegylated liposomal doxorubicin (PLD) vs. PLD monotherapy.

Methods: Women with advanced-relapsed epithelial ovarian cancer were randomly assigned 1: 1 to intravenous infusions of either T + PLD (trabectedin 1.

Hepatic safety analysis of trabectedin: results of a pharmacokinetic study with trabectedin in patients with hepatic impairment and experience from a phase 3 clinical trial.

Purpose Trabectedin is metabolized by the liver and has been associated with transient, noncumulative transaminase elevation. Two recent studies further characterize hepatic tolerability with trabectedin therapy: a phase 1 pharmacokinetic study (Study #1004; NCT01273493) in patients with advanced malignancies and hepatic impairment (HI), and a phase 3 study (Study #3007; NCT01343277) of trabectedin vs. dacarbazine in patients with advanced sarcomas and normal hepatic function.

Long-term alpha-tocopherol supplementation is associated with lower serum vascular endothelial growth factor levels.

Background: We previously reported that daily supplementation with alpha-tocopherol reduced prostate cancer risk in a large, randomized trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. One potential mechanism explaining this is that alpha-tocopherol inhibited tumor angiogenesis, an effect demonstrated in animal models.

Patients And Methods: We evaluated whether long-term supplementation with alpha-tocopherol modified serum vascular endothelial growth factor (VEGF) levels, a cytokine integrally involved in angiogenesis, in men who were not diagnosed with cancer and had baseline and follow-up blood available.