IMPORTANCE When a novel drug is granted accelerated approval, both its on-label and off-label uses must be taken into account. OBJECTIVES To estimate the potential upper bound of off-label use of erdafitinib to treat advanced cancer with fibroblast growth factor receptor gene (FGFR) alterations, compare it to the upper bound of on-label use in urothelial cancer, and to review studies that may support off-label use. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study used frequency data on FGFR alterations by cancer type and the estimated number of deaths from all cancers for 2019 in the United States. Mortality statistics were used as surrogates for patients with advanced cancer. Analysis was conducted in May 2019. EXPOSURE Percentage of patients with an FGFR2 or FGFR3 alteration. MAIN OUTCOMES AND MEASURES Estimated number of patients with advanced cancer expressing an FGFR2 or FGFR3 alteration eligible for off-label use of erdafitinib by cancer type; number of studies investigating FGFR-targeting drugs for patients with cancer; and number of ongoing clinical trials on erdafitinib by cancer type. RESULTS A total of 15 cancer types had reported FGFR alterations. Of 455 440 estimated patients who died of cancer in 2019, 17 019 (3.7%) were estimated to have FGFR2 or FGFR3 alterations. Of these patients, 12 955 (76.1%) could be eligible for off-label treatment with erdafitinib. A total of 29 completed studies evaluated FGFR-targeting drugs in 11 cancer types, and 10 ongoing studies are studying erdafitinib for different oncological indications. CONCLUSIONS AND RELEVANCE This study indicates that the potential for off-label use of FGFR inhibitors such as erdafitinib spans a number of cancer types and a large patient population. Systematic trials exploring off-label uses may be desirable for drugs that target clear, identifiable molecular alterations because this may be more efficient than off-label use in identifying clinical scenarios where the agent has activity.

This study aimed to retrospectively evaluate a cohort of patients with prostate cancer and persistent urinary incontinence after radical prostatectomy. From January 2004 to December 2015, eighty-six individuals were identified to have received an AUS implant, provided by a private nonprofit HMO operating in Belo Horizonte, Brazil. On total, there were 91 AUS implants, with a median interval between radical prostatectomy and AUS implant of 3.6 years (IQR 1.9 to 5.5). The rate of AUS cumulative survival, after a median follow-up of 4.1 years (IQR 1.7-7.2 years), was 44% (n=40). The median survival of AUS implants was 2.9 years (IQR 0.5-7.9 years). Thirty-seven AUS implants (40.7%) resulted in grade III surgical complications. There were 5 deaths at 2.1, 4.7, 5.7, 5.7 and 6.5 years of follow-up, but none due to causes directly associated to the AUS implant. Persistent severe incontinence was documented in 14 (15.3%) additional patients. From the 51 AUS implants which resulted in grade III surgical complications or persistent severe incontinence, 24 (47.1%) underwent surgical revisions. Explantation of the sphincter or its components was observed in 6 cases (25.0%). Mechanical failure, described as fluid loss and/or inability to recycle the AUS device, was observed in 4 devices (16.7%). In conclusion, although AUS implants are recommended as the gold-standard treatment of severe urinary incontinence after prostatectomy, the observed high rates of malfunction and grade III adverse events are a matter of concern warranting further assessment on the safety and efficacy of these devices.

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IntroductionMany patients presenting with arrhythmias are treated with antiarrhythmic drug therapy. However, for some patients, usually survivors of previous serious ventricular arrhythmias, treatment implies the use of implantable cardioverter defibrillators (ICDs) and/or Cardiac Resynchronization Therapy (CRT) devices.MethodsThis retrospective study evaluated a cohort of patients with arrhythmia requiring the use of ICDs, CRT or ICDs + CRT from January 2004 to March 2018. Data from a private healthcare organization in Belo Horizonte, Brazil were used to assess all-cause mortality and the need for replacement of the device. Continuous variables were expressed as mean and standard deviation. Cox proportional regression model and Log-Rank test were used to adjust the survival curve.ResultsFive hundred and ninety-three patients were included in the study (median age 67.6 years, range 23 to 89 years; male 62 percent). According to the type of device used to treat these patients, the distribution was 338 (57.0 percent), 169 (28.5 percent), 86 (14.5 percent), for ICDs, ICDs + CRT, CRT, respectively. After a mean follow-up time of 3.12 years (range 0 to 13.6 years), 283 devices were replaced (ICDs n = 140; ICDs + CRT n = 90; CRT n = 53) and 284 deaths occurred (median survival of 6.9 years). The median survival was 7.3, 5.8, 4.8, 5.5 years for ICDs single-chamber, ICDs dual-chamber, ICDs + CRT, CRT, respectively.ConclusionsRandomized trials are often criticized for their enrollment of highly selected patients. Studies on real-word data can provide reliable information regarding the use of ICDs and/or CRT devices in the treatment of patients with serious ventricular arrhythmias.

INTRODUCTION:Severe aortic stenosis with symptoms or left ventricular dysfunction has commonly a poor prognosis. Aortic valve replacement is usually performed for these patients aiming at improving their functional class and survival rate. Transcatheter aortic valve implantation (TAVI) is often presented as an option in patients with high surgical risk for conventional surgical valve replacement.(1) Nonetheless, in this group of patients, the literature has yielded conflicting evidence suggesting that benefits of TAVI for patients of high or intermediate surgical risk is not consistent.(2,3)METHODOLOGY:This retrospective study aimed to evaluate the mortality rate from a cohort of patients after the correction of aortic valve dysfunction with TAVI. It consisted of a convenience sample of patients at high risk for open surgery for the correction of aortic valve dysfunction treated with TAVI from 2013 to 2016. All included patients were being provided healthcare assistance by a private nonprofit health maintenance organization (HMO) operating in Belo Horizonte, Brazil. Since TAVI is not currently covered by the Brazilian supplementary healthcare system, reimbursements were enforced by lawsuits. Data was extracted from an administrative database, using the software Oracle Business Intelligence®. Continuous variables were expressed as mean and standard deviation. The Kaplan-Meier method was used to adjust the 1-year survival curve using the software STATA 13.1 (Stata Corp, College Station, TX, USA). This historical cohort resulted in no interventions, neither during the course of the instituted treatment nor after the observed outcome. Privacy of subjects and the confidentiality of their personal information were handled in accordance to the ethical principles of the Declaration of Helsinki.RESULTS:Overall, seventeen patients with a mean age of 80.5 years (68-91) underwent TAVI; 59 percent were women. Peri-operative mortality rate was 23.5 percent (n = 4) and accumulated overall one-year mortality was 35.3 percent (n = 6). Mean length of hospital stay was 26.9 ± 16.6 days. Prolonged hospital stay (≥ 7 days) occurred in 14/17 cases (82.3 percent), with a maximum of 51 days.CONCLUSIONS:In similarity to our findings, other authors described a high early and late mortality rate in patients undergoing TAVI. The strategy to use TAVI as an alternative in patients at high risk for open surgery is still under debate and should be carefully discussed taking into consideration the local team expertise as well as local healthcare available recourses.