Prognostic impact of FGFR2/3 alterations in patients with biliary tract cancers receiving systemic chemotherapy: the BITCOIN study.

AIM: FGFR2 rearrangements have been identified as a novel therapeutic target of biliary tract cancer (BTC). However, reliable prevalence estimates of this molecular alteration and its prognostic role have not been fully elucidated. METHODS: A retrospective mono-institutional series of 286 patients affected by locally advanced or metastatic BTC (183 intrahepatic cholangiocarcinomas, 67 extrahepatic cholangiocarcinomas, 36 gallbladder carcinomas) was profiled by means of targeted DNA/RNA next-generation sequencing, immunohistochemistry and fluorescence in situ hybridisation for FGFR2/3, ERBB2, NTRK alterations, IDH1/2 and BRAF mutations and DNA mismatch repair complex proteins alterations/microsatellite instability. RESULTS: FGFR2 rearrangements, amplifications and point mutations were detected in 15 (5.2%), 1 and 3 cases, respectively. FGFR3 alterations were observed in 5 (1.7%) cases. IDH1/2 were mutated in 35/223 cases (15.7%). A total of 9/258 (3.5%) and 6/260 (2.3%) BTCs had ERBB2 and BRAF gene alterations, respectively. Two cases (2/242; 0.8%) had NTRK1 amplifications but no rearrangement was found. A deficit of mismatch repair protein expression was identified in 9/237 cases (3.8%). At multivariate analysis, age, ECOG performance status, number of metastatic sites, tumour stage, FGFR2/3 alterations and IDH1/2 mutations were prognostic factors of overall survival. CONCLUSIONS: These data provide a strong proof - challenged with a robust and detailed multivariate model - that FGFR2/3 aberrations (including FGFR2 rearrangements) and IDH1/2 mutations can be prognostic for better survival in patients with BTC . The recognition and the measurement of their prognostic impact could be of primary importance for the correct interpretation of currently available data and in the design of new therapeutic trials.

Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma.

INTRODUCTION: To describe the efficacy of infigratinib, a potent, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, across lines of therapy (LOT) in patients with metastatic urothelial cancer (mUC). PATIENTS AND METHODS: Eligible patients had mUC and prior platinum-based chemotherapy, unless contraindicated, and activating FGFR3 mutation/fusion. Patients received infigratinib 125 mg orally daily (3 weeks on/1 week off) in a single-arm, open-label study. Primary endpoint: investigator-assessed confirmed objective response rate (ORR). Disease control rate (DCR), progression-free survival (PFS), best overall response (BOR) that included unconfirmed responses, and overall survival (OS) were also assessed. Subgroup analysis of efficacy and safety outcomes by LOT was performed. RESULTS: Sixty-seven patients were enrolled; 13 (19.4%) received infigratinib as early-line therapy for mUC due to ineligibility to receive platinum-based chemotherapy. Overall, ORR was 25.4% (95% CI 15.5-37.5) and DCR was 64.2% (95% CI 51.5-75.5). ORR was 30.8% (95% CI 9.1-61.4) with early-line infigratinib and 24.1% (95% CI 13.5-37.6) for ≥2 LOT. DCR was 46.2% (95% CI 19.2-74.9) for early-line and 68.5% (95% CI 54.4-80.5) for ≥2 LOT. PFS and OS appeared similar in both groups. Thirteen of 59 patients with a bladder primary tumor received early-line treatment with an ORR of 30.5% (95% CI 9.1-61.4), and 46 received ≥2 LOT with an ORR of 20.3% (95% CI 9.4-33.9); BOR was 38.5% (95% CI: 13.9-68.4%) and 42.6% (95% CI: 29.2-56.8%) in the early-line and salvage settings, respectively. Eight patients with upper tract urothelial carcinoma received salvage therapy (ORR, 50.0%; DCR, 100.0%). No significant differences in toxicities between LOT were observed. CONCLUSION: Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC.

Hyperphosphatemia Secondary to the Selective Fibroblast Growth Factor Receptor 1-3 Inhibitor Infigratinib (BGJ398) Is Associated with Antitumor Efficacy in Fibroblast Growth Factor Receptor 3-altered Advanced/Metastatic Urothelial Carcinoma.

BACKGROUND: Infigratinib (BGJ398) is a potent, selective fibroblast growth factor receptor (FGFR) 1-3 inhibitor with significant activity in metastatic urothelial carcinoma (mUC) bearing FGFR3 alterations. It can cause hyperphosphatemia due to the "on-target" class effect of FGFR1 inhibition. OBJECTIVE: To investigate the relationship between hyperphosphatemia and treatment response in patients with mUC. INTERVENTION: Oral infigratinib 125 mg/d for 21 d every 28 d. DESIGN, SETTING, AND PARTICIPANTS: Data from patients treated with infigratinib in a phase I trial with platinum-refractory mUC and activating FGFR3 alterations were retrospectively analyzed for clinical efficacy in relation to serum hyperphosphatemia. The relationship between plasma infigratinib concentration and phosphorous levels was also assessed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical outcomes were compared in groups with/without hyperphosphatemia. RESULTS AND LIMITATIONS: Of the 67 patients enrolled, 48 (71.6%) had hyperphosphatemia on one or more laboratory tests. Findings in patients with versus without hyperphosphatemia were the following: overall response rate 33.3% (95% confidence interval [CI] 20.4-48.4) versus 5.3% (95% CI 0.1-26.0); disease control rate 75.0% (95% CI 60.4-86.4) versus 36.8% (95% CI 16.3-61.6). This trend was maintained in a 1-mo landmark analysis. Pharmacokinetic/pharmacodynamic analysis showed that serum phosphorus levels and physiologic infigratinib concentrations were correlated positively. Key limitations include retrospective design, lack of comparator, and limited sample size. CONCLUSIONS: This is the first published study to suggest that hyperphosphatemia caused by FGFR inhibitors, such as infigratinib, can be a surrogate biomarker for treatment response. These findings are consistent with other reported observations and will need to be validated further in a larger prospective trial. PATIENT SUMMARY: Targeted therapy is a new paradigm in treating bladder cancer. In a study using infigratinib, a drug that targets mutations in a gene called fibroblast growth factor receptor 3 (FGFR3), we found that elevated levels of phosphorous were associated with greater clinical benefit. In the future, these data may help inform treatment strategies.

"They're on the Fast Track": Older Blacks Describe Experiences of Nursing Care Quality During Hospitalization.

Older Black patients are at increased risk for experiencing a hospital readmission. This disparity may be related to a variety of factors, including care received during hospitalization. The purpose of this study was to elicit the perceptions of older Black patients at high risk for readmission, and explore their nursing care needs and preferences during and following hospitalization. A qualitative descriptive design was used, including individual interviews with 19 Black members of a Program of All-Inclusive Care for the Elderly facility located in a northeastern urban setting. Four themes were captured encompassing characteristics of nursing care quality, unmet care needs, nurse-patient communication, and observations of competing nursing demands. Efforts to improve care transitions and prevent readmissions must address the needs and preferences of high-risk older Black patients while also attending to system-level inefficiencies that decrease the ability for nurses to complete all aspects of care.

Cultural Competency Training to Increase Minority Enrollment into Radiation Therapy Clinical Trials-an NRG Oncology RTOG Study.

Despite initiatives to increase the enrollment of racial and ethnic minorities into cancer clinical trials in the National Cancer Institute National Cancer Clinical Trials Network (NCCTN), participation by Latino and African American populations remain low. The primary aims of this pilot study are (1) to develop a Cultural Competency and Recruitment Training Program (CCRTP) for physician investigators and clinical research associates (CRAs), (2) to determine if the CCRTP increases cultural competency scores among physician investigators and CRAs, and (3) to determine the impact of the CCRTP on minority patient recruitment into NRG Oncology Radiation Therapy Oncology Group (RTOG) clinical trials. Sixty-seven CRAs and physicians participated in an in-person or online 4-h CRRTP training. Five knowledge and attitude items showed significant improvements from pre- to post-training. A comparison between enrolling sites that did and did not participate in the CCRTP demonstrated a pre to 1-year post-incremental increase in minority accrual to clinical trials of 1.2 % among participating sites. While not statistically significant, this increase translated into an additional 300 minority patients accrued to NCCTN clinical trials in the year following the training from those sites who participated in the training.

Unmet Nursing Care Linked to Rehospitalizations Among Older Black AMI Patients: A Cross-Sectional Study of US Hospitals.

BACKGROUND: Recent studies suggest that nurses may be unable to complete all aspects of necessary care due to a lack of time. Research is needed to determine whether unmet nursing care contributes to disparities in readmissions for vulnerable populations. OBJECTIVES: To examine differences in the relationship between nursing care left undone and acute myocardial infarction readmissions among older black patients compared with older white patients. RESEARCH DESIGN: Cross-sectional analysis of multiple datasets, including: 2006 to 2007 administrative discharge data, a survey of registered nurses, and the American Hospital Association Annual Survey. Risk-adjusted logistic regression models were used to estimate the association between care left undone and 30-day readmission. Interactions were used to examine the moderating effect of care left undone on readmission by race. RESULTS: The sample included 69,065 patients in 253 hospitals in California, New Jersey, and Pennsylvania. Older black patients were 18% more likely to experience a readmission after adjusting for patient and hospital characteristics and more likely to be in hospitals where nursing care was often left undone. Black patients were more likely to be readmitted when nurses were unable to talk/comfort patients [odds ratio (OR), 1.09; 95% confidence interval (CI), 1.01-1.19], complete documentation (OR, 1.16; 95% CI, 1.01-1.32), or administer medications in a timely manner (OR, 1.26; 95% CI, 1.09-1.46). CONCLUSIONS: Unmet nursing care is associated with readmissions for older black patients following acute myocardial infarction. Investment in nursing resources to improve the delivery of nursing care may decrease disparities in readmission.

Magnet® Hospital Recognition Linked to Lower Central Line-Associated Bloodstream Infection Rates.

Central-line-associated bloodstream infections (CLABSI) are among the deadliest heathcare-associated infections, with an estimated 12-25% mortality rate. In 2014, the Centers for Medicare and Medicaid Services (CMS) began to penalize hospitals for poor performance with respect to selected hospital-acquired conditions, including CLABSI. A structural factor associated with high-quality nursing care and better patient outcomes is The Magnet Recognition Program®. The purpose of this study was to explore the relationship between Magnet status and hospital CLABSI rates. We used propensity score matching to match Magnet and non-Magnet hospitals with similar hospital characteristics. In a matched sample of 291 Magnet hospitals and 291 non-Magnet hospitals, logistic regression models were used to examine whether there was a link between Magnet status and CLABSI rates. Both before and after matching, Magnet hospital status was associated with better (lower than the national average) CLABSI rates (OR = 1.60, 95%CI: 1.10, 2.33 after matching). While established programs such as Magnet recognition are consistently correlated with high-quality nursing work environments and positive patient outcomes, additional research is needed to determine whether Magnet designation produces positive patient outcomes or rewards existing excellence.

Examining Differences in Opportunity and Eligibility for Cancer Clinical Trial Participation Based on Sociodemographic and Disease Characteristics.

PURPOSE/OBJECTIVES: To examine differences in opportunity and eligibility for cancer clinical trial (CCT) participation based on sociodemographic and disease characteristics.
. DESIGN: A matched cross-sectional study including a prospective oral questionnaire and retrospective electronic medical record (EMR) review.
. SETTING: A single hospital in a large academic National Cancer Institute-designated cancer center in Philadelphia, Pennsylvania.
. SAMPLE: 44 Black or Hispanic and 44 Non-Hispanic White newly diagnosed individuals matched on cancer type and age (plus or minus five years).
. METHODS: Participants answered a questionnaire to capture self-reported opportunity for CCT participation, sociodemographic information, and cancer type. With consent, the authors completed a retrospective review of the EMR to assess eligibility and collect cancer stage and performance status.
. MAIN RESEARCH VARIABLES: Opportunity and eligibility for CCT participation.
. FINDINGS: Most participants (78%) had no opportunity for participation and were ineligible for all available trials. No differences were noted in opportunity for participation or eligibility based on race or ethnicity. Participants with late-stage disease were more likely to have opportunity and be eligible for CCT participation (p = 0.001). Those with private insurance were less likely to have opportunity for participation (p = 0.05).
. CONCLUSIONS: Limited trial availability and ineligibility negatively influenced opportunity for CCT participation for all populations. Levels of under-representation for CCT participation likely vary within and across sociodemographic and disease characteristics, as well as across healthcare settings.
. IMPLICATIONS FOR NURSING: The unique roles of nurse navigators and advanced practice nurses can be leveraged to increase opportunities for CCT participation for all populations.