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Background: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. Methods: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). Results: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation. Conclusions: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment. Clinical trial registration: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012). Key points: • The follow-up (104-week) results of the JUMPs study showed that the rate of treatment discontinuation (range: 71–81%) and resolution of symptoms (range: 43–47%) were similar among Japanese patients with schizophrenia treated with aripiprazole, blonanserin, and paliperidone. • Continued second-generation antipsychotic treatment (104-week) contributes to the maintenance of remission, social functioning, and QOL. • Treatment discontinuation is likely to get affected by shorter disease duration and higher dose of antipsychotics (chlorpromazine-equivalent antipsychotic dosage level: ≥1000 mg) before switching to single treatment with any of the three second-generation antipsychotics. [ABSTRACT FROM AUTHOR]

Abstract Background We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study. Methods JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension). Results In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p

Abstract Background To report real-world outcomes of patients with primary Reghmatogenous Retinal Detachment (RRD) treated with Pneumatic Retinopexy (PnR) according to the indications of the Pneumatic Retinopexy versus Vitrectomy for management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) trial. Methods Multicenter, retrospective study. Patients treated with PnR for RRD between 2021 and 2023 and a follow-up of at least 6 months were included. Single-procedure anatomical success, final anatomical success, complications, causes of failures, best corrected visual acuity (BCVA) after surgery, and the vision-related quality of life using the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were reported. Results A total of 76 eyes of 76 patients were included. Mean age was 60 ± 8.1 years. Primary anatomic reattachment was achieved by 84.3% of patients and final anatomical reattachment after pars plana vitrectomy was obtained in 100% of patients. BCVA improved from 0.32 (20/40) to 0.04 (20/20) logMar (p

Background: To report real-world outcomes of patients with primary Reghmatogenous Retinal Detachment (RRD) treated with Pneumatic Retinopexy (PnR) according to the indications of the Pneumatic Retinopexy versus Vitrectomy for management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) trial. Methods: Multicenter, retrospective study. Patients treated with PnR for RRD between 2021 and 2023 and a follow-up of at least 6 months were included. Single-procedure anatomical success, final anatomical success, complications, causes of failures, best corrected visual acuity (BCVA) after surgery, and the vision-related quality of life using the 25-Item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were reported. Results: A total of 76 eyes of 76 patients were included. Mean age was 60 ± 8.1 years. Primary anatomic reattachment was achieved by 84.3% of patients and final anatomical reattachment after pars plana vitrectomy was obtained in 100% of patients. BCVA improved from 0.32 (20/40) to 0.04 (20/20) logMar (p < 0.001) at 6 months. The main cause of failure was related to the presence of additional (likely missed) retinal breaks (66.6% of cases). Also, primary PnR failure was more frequent in eyes of patients with older age, macular involvement, worse baseline BCVA, greater extent of the RRD, and increased duration from diagnosis to treatment. Overall, the mean NEI-VFQ 25 composite score was 93.9% ± 6.4 at 6 months. Conclusions: The criteria of the PIVOT trial can be applied to real-world scenarios in the decision-making process for the treatment of primary RRD, with excellent anatomical and functional outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the disparity between the efficacy observed in clinical trials and effectiveness in real-world practice (efficacy-effectiveness gap (EE gap)) in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx between 2008 and 2016, were captured. Median overall survival (mOS) of gemcitabine + cisplatin (GemCis)-patients was 10.4 months (95%-CI 7.9–13.0), which was shorter compared to clinical trial findings (range mOS: 12.7–14.3 months) despite comparable clinical characteristics. An EE gap seems present. The mOS of gemcitabine + carboplatin (GemCarbo)-patients was 9.3 months (95%-CI 7.5–11.1). GemCarbo patients had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all p-values < 0.001)) compared to GemCis patients, but survival was not statistically significant different in a multivariable regression analysis (HR 0.90 (95%-CI 0.55–1.47), p-value = 0.674). [ABSTRACT FROM AUTHOR]

Aim: Fedratinib is an oral selective JAK2 inhibitor approved in the USA for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis (MF). Methods: This observational study assessed adult US patients who received ruxolitinib for primary MF (Flatiron Health database: 1 January 2011–31 October 2020). Patients were stratified by post-ruxolitinib treatment (fedratinib vs non-fedratinib). Results: Characteristics were comparable between fedratinib (n=70) and non-fedratinib (n=159) groups (median age: 71.0 vs 70.0 years; females: 55.7 vs 50.3%; median follow-up: 7.0 vs 6.0 months). Median overall survival (not reached vs 17 months) and 12 month survival (71.6 vs 53.5%) were improved with fedratinib versus the non-fedratinib therapies. Conclusion: In MF patients who received frontline ruxolitinib, survival was improved with subsequent fedratinib versus non-fedratinib care. Real-world outcomes show that in patients with primary myelofibrosis in the US, who received frontline ruxolitinib, survival was improved with subsequent fedratinib, an oral selective JAK2 inhibitor, versus non-fedratinib care. Until relatively recently, the nonselective JAK1/JAK2 inhibitor ruxolitinib was the only pharmacological therapy available for primary myelofibrosis (MF). In August 2019, the US FDA approved the selective JAK2 inhibitor fedratinib for use in patients with MF who had previously received ruxolitinib. This retrospective, observational study used patient-level data from the Flatiron Health database to identify patients with MF who discontinued ruxolitinib between 1 January 2011 and 31 October 2020 and subsequently received either fedratinib (fedratinib group) or non-fedratinib therapies (non-fedratinib group); a sensitivity analysis assessed a subgroup within the non-fedratinib group that discontinued ruxolitinib after FDA approval in August 2019 (contemporary non-fedratinib subgroup). Patients were followed until death, loss to follow-up or end of study period; baseline demographics and clinical characteristics were compared between groups, and survival was calculated as time from index until death or censoring. We identified 229 patients who discontinued ruxolitinib therapy for MF, including 70 who subsequently received fedratinib (fedratinib group: n = 70; a non-fedratinib group: n = 159); the latter group included 109 patients belonging to the non-fedratinib contemporary subgroup. Baseline patient demographic characteristics were broadly comparable between the groups, and overall survival appeared to be improved in the fedratinib group versus the non-fedratinib group and the contemporary non-fedratinib subgroup. In patients with primary MF who discontinue ruxolitinib, fedratinib therapy appears to confer substantial survival benefits compared with other, non-fedratinib therapies. [ABSTRACT FROM AUTHOR]

Given the treatment landscape evolution for aRCC, real-world data are needed. All French patients newly treated for aRCC initiated in 2016 were included. In first-line, patients were mainly treated with sunitinib, and in secondline half were treated with nivolumab. The highest OS was observed for patients treated with sunitinib in firstline and for patients treated with nivolumab in second-line. Background: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment. Materials and Methods: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS). The first-line treatment initiation date constituted the index date and patients were followed until death, loss to follow-up, or December 31, 2019, whichever occurred first. aRCC was identified using hospital diagnosis, long-term disease, or renal biopsy before index date. All analyses were performed for first and second-line treatment. Overall survival (OS) and time-to-next treatment or death (TNT-D) were estimated using Kaplan-Meier approach. Results: In 2016, 1629 patients initiated a first-line treatment for aRCC. Most of them were male (75.9%) and the median age was 67 years. Most of patients (91.7%) had received a tyrosine kinase inhibitor as first-line treatment, mainly sunitinib (64.4%), and 53.5% received a second-line, among which 43.7% nivolumab. Median OS (95% confidence interval [CI]) was 20.7 (95% CI:18.2-22.4) months from first-line treatment initiation and 15.4 (13.9-17.5) months from second-line treatment initiation. Median TNT-D were respectively 9.3 (9.7-12.1) months and 6.9 (5.9-7.7) months. Conclusion: This study highlights the limited survival of aRCC patients These results provide a valuable baseline and highlight the need for innovation, such as immune checkpoint inhibitor-based combinations that have recently became first-line standard of care. [ABSTRACT FROM AUTHOR]

Objectives: Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in lung cancers, long considered untargetable, have had a recent rise in interest due to promising data of agents targeting KRAS p.G12C. As Indian data are scarce, we sought to identify baseline clinical characteristics, prognostic factors and outcomes of lung cancer patients with KRAS mutations at our hospital. Methods: Patients with KRAS mutant lung cancers treated at our institute from 2016 to 2022 were analysed. Results: 133 patients with KRAS mutant lung cancers were identified. Median age was 57 (interquartile range 28-78) years, and 58 (43.6%) were smokers. 17 (12.7%) had brain metastases. The commonest variant was p.G12C, seen in 53 (39.8%) patients. Six (4.5%) had programmed death ligand 1 (PDL-1) expression >50% by Ventana SP263 PDL-1 assay, and 13 (9.7%) had epidermal growth factor mutation. Of 92 patients with available treatment details, the majority received intravenous chemotherapy, nine (9.8%) received tyrosine kinase inhibitors and four (4.4%) received immunotherapy (pembrolizumab). Median progression-free survival (PFS) with first-line therapy was 6 (95% confidence interval (CI) 2.8-9.2) months and median overall survival (OS) was 12 (CI 9.2-14.8) months. The incidence of brain metastases was higher in patients with G12C mutations (p = 0.025). Brain metastases (HR: 3.57, p < 0.001), Eastern Cooperative Oncology Group performance status (PS) = 2 (HR: 2.13, p = 0.002) and G12C mutation (HR: 1.84, p = 0.011) were associated with inferior PFS, while brain metastases (HR: 4.6, p < 0.001), PS = 2 (HR: 2.33, p = 0.001) and G12C mutation (HR: 1.93, p = 0.01) were associated with inferior OS. Conclusion: This is the largest dataset of KRAS mutant lung cancers from India. Brain metastases were higher in patients with G12C mutations and associated with poorer PFS and OS. G12C mutation and PS = 2 were also associated with inferior PFS and OS. Experience with targeted therapy for KRAS mutations remains an area of future exploration due to the unavailability of these agents in India. [ABSTRACT FROM AUTHOR]

Background: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. Methods: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. Results: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤.01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P =.01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. Conclusion: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC. This article evaluates real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. [ABSTRACT FROM AUTHOR]

Background: To report the outcomes of low‐dose atropine (0.01% and 0.05%) for preventing myopia progression in a real‐world Australian cohort during the COVID‐19 pandemic. Methods: Records of children presenting with myopia, from January 2016 to 2022, were retrospectively reviewed at a comprehensive ophthalmic practice. Children who discontinued treatment, ages >18, and cases with hereditary conditions were excluded. The rate of progression of myopia after treatment with atropine was compared with historical data to evaluate the effectiveness of the regime. Results: One hundred and one children (mean baseline spherical equivalent [SphE] [−3.70 +/− 2.09 D] and axial length [AL] [24.59 +/− 1.00 mm]) were analysed. The mean age of the children was 10.4 +/− 2.89 years and 61% were females. The average follow‐up time was 17.9 +/− 12.5 months. The mean rate of progression of AL and SphE on 0.01% atropine eyedrops was 0.219 +/− 0.35 mm and − 0.250 +/− 0.86 D/year, respectively. 68.1% of the children treated with 0.01% atropine were mild progressors (<0.5 D change/year). Non‐responders when commenced on a higher dose of atropine (0.05%) experienced a 93% (p = 0.012) and 30% reduction in SphE and AL growth rate, respectively. Family history, higher myopia or younger age at baseline and shorter duration of treatment were associated with steeper progression (p < 0.01). Both doses were well tolerated. Conclusions: Low‐dose atropine was shown to be beneficial in a real‐world clinical setting, despite interruptions to follow‐ups secondary to COVID‐19 pandemic. A 0.05% dose of atropine may be effective in cases where 0.01% was ineffective. [ABSTRACT FROM AUTHOR]

(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in EGFR or HER2 were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan–Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the EGFR cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not (p < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; p = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST (p = 0.744). For the HER2 cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not (p = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not (p = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST (p = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among HER2 ex20ins patients who received ex20ins-specific TKIs.

Background: For eligible patients with unresectable stage III non-small-cell lung cancer, durvalumab consolidation therapy following chemoradiotherapy is the standard of care. Methods: This was a retrospective study of durvalumab-treated patients diagnosed between 1 August 2017 and 29 February 2020. Electronic health record data were assessed descriptively, with Kaplan–Meier methods used for duration of treatment and overall survival (OS). Results: Among 528 patients (median age 70 years, 51.5% male), the median duration of treatment was 7.1 months (95% CI: 6.0–9.0). Estimated 1- and 2-year OS rates were 83.5 and 64.0%, respectively, with median OS not reached. Conclusion: This study confirmed an OS benefit with durvalumab after chemoradiotherapy in a real-world setting, consistent with the results from the PACIFIC phase III clinical trial. Durvalumab is a treatment approved for patients with a specific type of lung cancer. Clinical trials have shown durvalumab is an effective therapy for these patients. We conducted this study to better understand what happens to patients treated with durvalumab who were not enrolled in clinical trials. Patients who were treated with durvalumab in this study tended to survive as long as patients who received it as part of a clinical trial. Studies like this one may better represent patients who are less likely to take part in clinical trials. Future studies may examine long-term outcomes of durvalumab and factors associated with better outcomes. [ABSTRACT FROM AUTHOR]

(1) Background: Exon 20 insertion mutations (ex20ins) in EGFR and HER2 are uncommon driver mutations in non-small-cell lung cancer (NSCLC), with a poor prognosis and few targeted therapy options, and there are limited real-world data. Here, we report the clinicopathologic features and outcomes for patients with ex20ins NSCLC across British Columbia, Canada. (2) Methods: NSCLC patients with ex20ins in EGFR or HER2 were identified via tumour testing between 1 January 2016 and 31 December 2021 (n = 7233). Data were collected by chart review. Survival analyses were performed using the Kaplan–Meier method using the log-rank test. (3) Results: A total of 131 patients were identified. The median age was 66. Thirty-three percent of patients had brain metastases. For the EGFR cohort, the median OS was 18.6 months for patients who received any systemic therapy (ST) vs. 2.6 months for patients who did not (p < 0.001). Median OS was similar for patients treated with ex20ins-specific tyrosine kinase inhibitors (TKIs) vs. other STs (18.6 vs. 15.9 months; p = 0.463). The median first-line PFS was 4.1 vs. 7.4 months for patients treated with a TKI vs. other ST (p = 0.744). For the HER2 cohort, the median OS was 9.0 months for patients who received any ST vs. 4.9 months for patients who did not (p = 0.015). The median OS was 23.0 months for patients treated with an ex20ins TKI vs. 5.6 months for patients who were not (p = 0.019). The median first-line PFS was 5.4 vs. 2.1 months for patients treated with a TKI vs. other ST (p = 0.343). (4) Conclusions: Overall survival was significantly longer among ex20ins patients who received any systemic therapy vs. those who did not. Overall survival was significantly better among HER2 ex20ins patients who received ex20ins-specific TKIs. [ABSTRACT FROM AUTHOR]

Background: Bevacizumab-awwb (MVASI®) was the first U.S. Food and Drug Administration-approved biosimilar to Avastin® (reference product [RP]) for the treatment of several different types of cancers, including metastatic colorectal cancer (mCRC), an indication approved based on extrapolation. Objectives: Evaluate treatment outcomes in mCRC patients who received first-line (1L) bevacizumab-awwb at treatment initiation or as continuing bevacizumab therapy (switched from RP). Design: A retrospective chart review study. Methods: Adult patients who had a confirmed diagnosis of mCRC (initial presentation of CRC on or after 01 January 2018) and initiated 1L bevacizumab-awwb between 19 July 2019 and 30 April 2020 were identified from the ConcertAI Oncology Dataset. A chart review was conducted to evaluate patient baseline clinical characteristics and effectiveness and tolerability outcomes during the follow-up. Study measures were reported stratified by prior use of RP: (1) naïve patients and (2) switchers (patients who switched to bevacizumab-awwb from RP without advancing the line of therapy). Results: At the end of study period, naïve patients (n = 129) had a median 1L progression-free survival (PFS) of 8.6 months [95% confidence interval (CI), 7.6–9.9] and a 12-month overall survival (OS) probability of 71.4% (95% CI, 61.0–79.5%). Switchers (n = 105) had a median 1L PFS of 14.1 months (95% CI, 12.1–15.8) and a 12-month OS probability of 87.6% (95% CI, 79.1–92.8%). During treatment with bevacizumab-awwb, 20 events of interest (EOIs) were reported in 18 naïve patients (14.0%) and 4 EOIs reported in 4 switchers (3.8%), of which the most commonly reported events were thromboembolic and hemorrhagic events. Most EOIs resulted in emergency department visit and/or treatment hold/discontinuation/switch. None of the EOIs resulted in death. Conclusion: In this real-world cohort of mCRC patients who were treated 1L with a bevacizumab biosimilar (bevacizumab-awwb), the clinical effectiveness and tolerability data were as expected and consistent with previously published findings from real-world studies of bevacizumab RP in mCRC patients. [ABSTRACT FROM AUTHOR]

Purpose: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy–effectiveness gap). The purpose of this study was to evaluate the efficacy–effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. Methods: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). Results: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9–13.0], which was shorter compared to clinical trial findings (range mOS: 12.7–14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5–11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55–1.47], P-value = 0.674). Conclusion: There seems to be an efficacy–effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics. [ABSTRACT FROM AUTHOR]

Abstract Introduction Belantamab mafodotin (BM) is a new anti-BCMA antibody–drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). Methods We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). Results Thirty-three patients were included with a median of 70 years of age (range, 46–79 years). Median time from diagnosis was 71 months (range, 10–858 months). Median prior lines was 5 (range, 3–8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1–16 doses), with a median follow-up of 11 months (6–15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92–5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10–0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107–740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient’s decision (3%). Conclusions BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Abstract Background A majority of patients undergoing curative intent surgery for pancreatic ductal adenocarcinoma (PDAC) will unfortunately develop recurrent disease. Treatment outcomes for patients with metastatic disease remain suboptimal. In this study, we evaluated clinical outcomes of patients with recurrent PDAC who received systemic therapy and compared outcomes to patients with de novo metastatic PDAC undergoing systemic therapy. Methods Patients diagnosed with metastatic PDAC between 2014 and 2019 were included using a real-world database. Patients were characterized as either de novo or recurrent based on the date of metastatic diagnosis and history of surgical resection. Overall survival (OS) was summarized within groups via Kaplan–Meier survival estimates and compared using Cox proportional hazards models. Results We included 5170 patients with metastatic PDAC, of which 1101 (21.3%) were classified as having recurrent disease. Median OS for the recurrent group was significantly greater at 10.8 m (95% CI 9.9–11.7) than in the de novo group at 7.3 m (95% CI 7.0–7.7, p

Acute lymphoblastic leukemia (ALL) is an aggressive bone marrow cancer with disparate outcomes. Data on patient outcomes in real world settings outside of clinical trials is limited. The current study reports on outcomes for 137 ALL patients who received an adult induction and consolidation regimen derived from the CALGB 10102 trial modified without alemtuzumab. Of the 137 patients, 32 were < 40 years old, 52 were between 40 and 59, and 53 were ≥ 60 years old. Overall, 109 (79.6%) patients achieved a complete remission (< 40: 96.1%, 40–59: 86.5%, and 62.3% ≥ 60 (p = 0.0002)). Progression free survival for the entire cohort was 13.5 months and by age was 19.8 months for less than 40, 23.4 months for 40 to 59 and 6.7 months for ≥ 60; p = 0.0002. Median survival was 22.1 months for the entire cohort (32.9 months for ages < 40, 26.6 months ages 40–59, 7.8 months ≥ 60, p < 0.001). [ABSTRACT FROM AUTHOR]

Context: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are used off-label in the management of type 1 diabetes mellitus (T1DM) in real-world practice as adjuvant therapies to insulin. There are few real-world data regarding efficacy and safety of this practice. Objective: This work aimed to determine the efficacy and safety of GLP-1RAs and sodium-glucose SGLT2is in the management of T1DM in realworld practice. Methods: A retrospective chart review was performed of all instances of GLP-1RA and/or SGLT2i use greater than 90 days in adult patients with T1DM at a single academic center. We report the clinical and safety outcomes over the duration of use. Results: We identified 104 patients with T1DM who ever used a GLP-1RA (76 patients) or SGLT2i (39 patients) for more than 90 days. After 1 year of therapy, GLP-1RA users had statistically significant reductions in weight (90.5 kg to 85.4 kg; P< .001), glycated hemoglobin A1c (HbA1c) (7.7% to 7.3%; P=.007), and total daily dose of insulin (61.8 units to 41.9 units; P<.001). SGLT2i users had statistically significant reductions in HbA1c (7.9% to 7.3%; P<.001) and basal insulin (31.3 units to 25.6 units; P=.003). GLP-1RA users compared to SGLT2i users had greater reduction in weight (P=.027) while HbA1c reduction was comparable between the groups. Over a mean total duration of use of 29.5 months/patient for both groups, more SGLT2i users experienced diabetic ketoacidosis (DKA) (12.8% vs 3.9%). Therapy was discontinued because of adverse events 26.9% of the time for GLP-1RA users vs 27.7% for SGLT2i users. Conclusion: GLP-1RA and SGLT2i use in T1DM is associated with clinically relevant benefits. DKA remains a clinical concern with SGLT2i use, requiring careful patient selection and monitoring, with the risk to benefit ratio of treatment evaluated at an individual level. [ABSTRACT FROM AUTHOR]

Introduction: Despite recent advances in diabetes technology, most people living with type 1 diabetes mellitus (T1D) are unable to meet glycemic targets. Real-world evidence can provide insight into outcomes achieved with specific treatment devices when used in clinical practice. The aim of this study was to analyze real-world outcomes collected from a large cohort of people living with T1D and initiating treatment with the Omnipod DASH System. Methods: In this retrospective observational study, real-world outcomes were analyzed from a database of information collected from people with T1D initiating the Omnipod DASH System. Information in the database was either taken directly from the patient's medical record or self-reported if medical records were unavailable. The primary outcome was change in glycated hemoglobin (HbA1c) from baseline (before initiation) to 3 months after initiation. Secondary outcomes were changes in total daily dose of insulin (TDD) and self-reported frequency of hypoglycemic events (< 70 mg/dL). Results are separated for the adult (≥ 18 years, N = 3341) and pediatric (< 18 years, N = 1397) cohorts. Results: The change in HbA1c from baseline was − 0.9 ± 1.6% (− 10 ± 18 mmol/mol; p < 0.0001) in adults and − 0.9 ± 2.0% (− 10 ± 22 mmol/mol; p < 0.0001) in the pediatric cohort. For those previously using multiple daily injections, HbA1c decreased by − 1.0 ± 1.7% (− 11 ± 19 mmol/mol) in adults and − 1.0 ± 2.1% (− 11 ± 23 mmol/mol) in the pediatric cohort (both p < 0.0001). Hypoglycemic events decreased in adults from 2.9 to 1.3 episodes per week (− 1.6 ± 3.2 events/week; p < 0.0001), and in the pediatric cohort from 2.8 to 1.5 episodes per week (− 1.3 ± 2.7 events/week; p < 0.0001). In adults, TDD decreased by 19.9% (p < 0.0001), and it remained stable in the pediatric cohort (p > 0.05). Conclusions: Real-world outcomes from this large cohort of people initiating therapy with the Omnipod DASH System showed significant improvement in HbA1c and a substantial reduction in hypoglycemic events after 3 months of use. [ABSTRACT FROM AUTHOR]

Introduction: Belantamab mafodotin (BM) is a new anti-BCMA antibody–drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). Methods: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). Results: Thirty-three patients were included with a median of 70 years of age (range, 46–79 years). Median time from diagnosis was 71 months (range, 10–858 months). Median prior lines was 5 (range, 3–8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1–16 doses), with a median follow-up of 11 months (6–15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92–5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10–0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107–740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). Conclusions: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the success of a clinic for subcutaneous administration of casirivmab and imdevimab (REGEN-COV; Regeneron) for treatment of patients with symptomatic mild to moderate coronavirus disease 2019 (COVID-19) in terms of preventing disease progression and healthcare utilization. Methods This retrospective single-center, propensity-matched cohort study examined healthcare utilization outcomes for patients who received subcutaneous casirivimab and imdevimab at a pharmacist-led clinic of an academic health system. Eligible patients were treated between August 1, 2021, and January 5, 2022, and were at high risk for COVID-19 disease progression. Treatment patients were propensity matched with high-risk control patients with a diagnosis of COVID-19 in the same timeframe who did not receive casirivimab and imdevimab. Patients were followed for 30 days for collection of data on inpatient admissions, emergency department visits, and mortality. Risk of a 30-day healthcare utilization event was assessed and tested for statistical significance utilizing McNemar's test. Results A total of 585 patients who received treatment with subcutaneous casirivimab and imdevimab were matched with 585 patients who did not receive casirivimab and imdevimab therapy. Patients who received casirivimab and imdevimab had significantly lower risk of a 30-day all-cause inpatient admission event than untreated patients (relative risk reduction, 62.4%; P < 0.0001). Treated patients also had a significantly lower risk of 30-day all-cause emergency department visit than untreated subjects (relative risk reduction, 36.5%; P = 0.0021). There were 6 mortality events in the untreated group and no mortality events in the treatment group. Conclusion This study provides evidence for the effectiveness of a subcutaneous casirivimab and imdevimab clinic in preventing progression of symptomatic mild to moderate COVID-19. [ABSTRACT FROM AUTHOR]

Background: Treatment of metastatic renal cell carcinoma (mRCC) is rapidly evolving with new combination therapies demonstrating improved response rates and survival. There are no head-to-head prospective trials comparing an immunotherapy doublet with an immunotherapy/tyrosine-kinase inhibitor-based combination. We compare real-world outcomes in patients treated with axitinib/pembrolizumab (axi/pembro) or ipilimumab/nivolumab (ipi/nivo). The primary endpoints were overall-survival (OS) and real-world progression-free survival (rwPFS). Patients and Methods: We used a de-identified database to select patients diagnosed with clear cell mRCC and treated with front-line axi/pembro or ipi/nivo from 2018 to 2022. Analyses are adjusted using propensity score-based inverse probability of treatment weighting, balancing age, gender, insurance, race, IMDC risk, and nephrectomy status. We compared survival by treatment groups using weighted and unweighted Kaplan–Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Results: We included a total of 1506 patients with mRCC who received frontline axi/pembro (n = 547) or ipi/nivo (n = 959). Median follow-up time was 20.0 months (range: 0.2-47.6). Baseline demographics were similar between the 2 cohorts. Adjusted median OS for the full population was 28.9 months for axi/pembro and was 24.3 months for ipi/nivo (P =.09). Twenty-four-month survival was 53.8% for axi/pembro treated patients and 50.2% for ipi/nivo treated patients. rwPFS was 10.6 months for axi/pembro treated patients and 6.9 months for ipi/nivo treated patients. Treatment with axi/pembro conferred improved survival in the IMDC favorable risk strata, with no significant difference in survival observed within the full cohort. Conclusions: In this retrospective, real-world study of patients treated with front-line combination therapy, patients with IMDC favorable risk disease had better survival when treated with axi/pembro compared to ipi/nivo. However, survival for the entire population and the 24-month median overall survival were not statistically different between treatment groups. Longer follow-up is necessary to discern any emerging significant differences. This article reports real-world outcomes of patients with metastatic renal cell carcinoma treated with combination therapies (either axitinib/pembrolizumab or ipilimumab/nivolumab).] [ABSTRACT FROM AUTHOR]

Fidaxomicin, a macrocyclic antibiotic, selectively kills Clostridioides difficile and reduces C. difficile infection (CDI) recurrence compared with vancomycin, but some studies and guidelines report fidaxomicin as being less cost-effective. The aim of this study was to compare the cost-effectiveness and budget impact of fidaxomicin versus vancomycin or metronidazole for treating CDI in a real-world UK setting. Data were retrospectively collected from medical records of 86 patients with CDI treated with vancomycin or metronidazole at a single UK hospital between April 2011 and March 2012, and prospectively from 62 patients with CDI treated with fidaxomicin between August 2012 and July 2013. CDI cases were matched by age, financial year, and healthcare resource use to control cases. CDI recurrence rates were lower with fidaxomicin (6.5%) than vancomycin/metronidazole (19.8%). An estimated 12 additional recurrent CDIs were prevented with fidaxomicin treatment. Patients with CDI had significantly higher healthcare costs than those without CDI, with a mean excess spend of GBP 10,748 and GBP 17,451 per patient in the fidaxomicin (p = 0.015) and vancomycin/metronidazole cohorts (p < 0.001), respectively. A second CDI was associated with mean excess costs of GBP 8373 and GBP 20,249 per patient in the fidaxomicin and vancomycin/metronidazole cohorts, respectively. Despite higher fidaxomicin drug costs, overall cost savings were estimated at GBP 140,292 (GBP 2125 per CDI). In this real-world study, first-line CDI treatment with fidaxomicin reduced healthcare costs versus vancomycin/metronidazole, consistent with previous studies. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognostic impact of FLT3–ITD allele ratio (AR) is a matter of controversy. We analyzed 2901 AML patients with long-term follow-up treated with PETHEMA protocols in the pre-FLT3 inhibitors era, with 579 of them harboring the FLT3–ITD mutation. We found that FLT3–ITD AR > 0.5 was associated with lower complete remission and rate and overall survival, while AR > 0.8 was associated with lower RFS. An AR of 0.44 was the best cutoff for OS and 0.8 for RFS. Overall, allo- and auto-hematopoietic stem cell transplant (HSCT) in first CR offered similar OS in patients with AR < 0.44, while allo-HSCT improved OS for those with higher AR. However, allo-HSCT resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3–ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5), supporting the use of other risk stratification tools, such as NPM1 MRD monitoring, in this setting. FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p < 0.001). Among NPM1/FLT3–ITD-mutated patients, median OS gradually decreased according to FLT3–ITD status and ratio (34.3 months FLT3–ITD-negative, 25.3 months up to 0.25, 14.5 months up to 0.5, and 10 months ≥ 0.5, p < 0.001). Post-remission allogeneic transplant (allo-HSCT) resulted in better OS and RFS as compared to auto-HSCT in NPM1/FLT3–ITD-mutated AML regardless of pre-established AR cutoff (≤0.5 vs. >0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR < 0.44 had similar 5-year OS after allo-HSCT or auto-HSCT (52% and 41%, respectively, p = 0.86), but worse RFS after auto-HSCT (p = 0.01). Among patients with FLT3–ITD AR > 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic pancreatic ductal adenocarcinoma (mPDAC) is a common cancer with poor survival outcomes. Although treatment options are limited, real-world treatment patterns and outcomes are not well understood, particularly beyond first-line treatment. This study described real-world treatment patterns and outcomes for mPDAC in the USA. Methods: This retrospective analysis used electronic health record-derived de-identified data of patients with mPDAC diagnosed between January 1, 2014 and June 30, 2021. Treatments were classified into six groups: (1) standard combination chemotherapy; (2) nonstandard combination chemotherapy; (3) single-agent chemotherapy; (4) targeted therapy; (5) clinical study drugs; and (6) off-label therapies. Analyses were descriptive in nature. Treatment utilization and switching, and time on treatment and time to discontinuation, were described by first-line (1LOT) and second-line (2LOT) treatment groups. Median overall survival (mOS) from 1LOT and 2LOT was stratified by treatment group, and for 1LOT on the basis of whether patients received further treatment. Results: 1LOT included 6979 patients, 3241 (46%) of whom received further 2LOT. Standard combination chemotherapy was the most common 1LOT (70%) and 2LOT (46%). Nonstandard combination chemotherapy was used more as 2LOT (35%) than 1LOT (11%). First-line time on treatment was generally higher than second-line time on treatment, and time to discontinuation was lower than time on treatment. mOS in days (months) from 1LOT was 271 (8.9), 252 (8.3), 219 (7.2), 170 (5.6), 280 (9.2), and 182 (6.0), and mOS from 2LOT was 202 (6.6), 193 (6.3), 186 (6.1), 193 (6.3), 179 (5.9), and 97 (3.2), for groups 1–6, respectively. Within group 1, mOS from 1LOT was 318 days (10.4 months) for FOLFIRINOX and 241 days (7.9 months) for gemcitabine and nab-paclitaxel. Conclusion: Most patients with mPDAC received 1LOT in line with clinical practice guidelines, yet mOS remains poor. This study highlights the need for novel therapies to demonstrate improved patient survival compared with therapies in current clinical practice guidelines. [ABSTRACT FROM AUTHOR]

Aim: Treatment options for triple-class exposed (TCE) patients with multiple myeloma (MM) in Japan are limited. Materials & methods: Retrospective observational study using the Medical Data Vision database (April 2008-April 2021). Eligible adults with MM received a new post-TCE treatment. Treatments, healthcare resource utilization (HCRU) and costs (per patient per month [PPPM]) were analyzed with subgroup analyses by prior stem cell transplantation (SCT vs No SCT). Results: Of 459 TCE patients, 216 (47%) had post-TCE treatment of whom 194 (90%) had no prior SCT. Median duration of the first post-TCE line of therapy (LOT) was 2 months; 49% of No SCT patients received a subsequent LOT. Total healthcare costs were comparable between No SCT and SCT groups (¥1.3 million PPPM each; US$12,328 and $12,391, respectively), driven by treatment costs. Median post-index overall survival (n = 216) was 15.8 months (95% CI: 10.5, 22.3). Conclusion: New treatments with better effectiveness are needed for patients with TCE MM in Japan. [ABSTRACT FROM AUTHOR]

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014–2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.

Mihaela Georgiana Musat,1 Christina Soeun Kwon,1 Elizabeth Masters,2 Slaven Sikirica,3 Debduth B Pijush,3 Anna Forsythe4 1Evidence Generation, Purple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc., Waltham, MA, USA; 2Real World Evidence, Pfizer, New York, NY, USA; 3Global Health Economics and Outcomes Research, Pfizer, New York, NY, USA; 4Value and Access, Purple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc., Waltham, MA, USACorrespondence: Mihaela Georgiana MusatPurple Squirrel Economics, a Wholly Owned Subsidiary of Cytel, Inc, 1050 Winter Street, Waltham, MA, 02451, USAEmail mihaela.musat@pshta.comBackground: To date, there has been limited synthesis of RWE studies in high-risk non-muscle invasive bladder cancer (HR-NMIBC). The objective of this research was to conduct a systematic review of published real-world evidence to better understand the real-world burden and treatment patterns in HR-NMIBC.Methods: An SLR was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with the scope defined by the Population, Intervention Comparators, Outcomes, and Study design (PICOS) criteria. EMBASE, MEDLINE, and Cochrane databases (Jan 2015–Jul 2020) were searched, and relevant congress abstracts (Jan 2018–Jul 2020) identified. The final analysis only included studies that enrolled ≥ 100 patients with HR-NMIBC from the US, Europe, Canada, and Australia.Results: The SLR identified 634 RWE publications in NMIBC, of which 160 studies reported data in HR-NMIBC. The average age of patients in the studies was 71 years, and 79% were males. The rates of BCG intravesical instillations ranged from 3% to 86% (29– 95% for induction and 8– 83% for maintenance treatment). Five-year outcomes were 17– 89% recurrence-free survival (longest survival in patients completing BCG maintenance), 58– 89% progression-free survival, 71– 96% cancer-specific survival (lowest survival in BCG-unresponsive patients), and 28– 90% overall survival (lowest survival in patients who did not receive BCG or instillation therapy).Conclusion: BCG treatment rates and survival outcomes in patients with HR-NMIBC vary in the real world, with better survival seen in patients completing maintenance BCG, responding to treatment, and not progressing to muscle-invasive disease. There is a need to better understand the factors associated with BCG use and discontinuation and for an effective treatment that improves outcomes in HR-NMIBC. Generalization of these results is limited by variations in data collection, reporting, and methodologies used across RWE studies.Keywords: real-world outcomes, high-risk NMIBC

Introduction: Limited-stage small-cell lung cancer (LS-SCLC) is potentially curable with concurrent chemoradiation (CRT). Cisplatin is the preferred platinum for the chemotherapy backbone in national guidelines. Unfortunately, many LS-SCLC patients are elderly, with comorbidities and poor performance status (PS), which preclude the use of cisplatin. Carboplatin may be a suitable alternative. This analysis evaluates the overall survival (OS) and time to next treatment (TTNT) in LS-SCLC patients receiving concurrent CRT by platinum use. Materials and methods: The study included LS-SCLC patients in the Flatiron Health nationwide de-identified electronic health record-derived database who received CRT in 2013–2019 with follow-up through May 2020. TTNT and OS were compared using both unadjusted and inverse propensity-weighted Cox proportional hazards models. Results: This study included patients treated with carboplatin (n = 600) or cisplatin (n = 572) in combination with etoposide and radiation. Cisplatin patients were younger, had a shorter time from diagnosis to radiation, and had less kidney disease. In an unadjusted analysis, median overall survival (mOS) was greater in the cisplatin group than the carboplatin group with mOS of 22.3 months vs. 19.2 months and Hazard Ratio (HR) of 0.83 (p = 0.01). In the inverse propensity-weighted analysis, this difference was no longer significant (HR 0.93, p = 0.37). No differences were seen in TTNT. Conclusion: When balancing on key clinical factors, we observed no statistical difference in OS or TTNT by platinum choice in real-world LS-SCLC patients treated with CRT. Although observational, the results from this large data set are consistent with the hypothesis that either cisplatin or carboplatin is an appropriate therapy regardless of health status.

Background: A majority of patients undergoing curative intent surgery for pancreatic ductal adenocarcinoma (PDAC) will unfortunately develop recurrent disease. Treatment outcomes for patients with metastatic disease remain suboptimal. In this study, we evaluated clinical outcomes of patients with recurrent PDAC who received systemic therapy and compared outcomes to patients with de novo metastatic PDAC undergoing systemic therapy.Methods: Patients diagnosed with metastatic PDAC between 2014 and 2019 were included using a real-world database. Patients were characterized as either de novo or recurrent based on the date of metastatic diagnosis and history of surgical resection. Overall survival (OS) was summarized within groups via Kaplan-Meier survival estimates and compared using Cox proportional hazards models.Results: We included 5170 patients with metastatic PDAC, of which 1101 (21.3%) were classified as having recurrent disease. Median OS for the recurrent group was significantly greater at 10.8 m (95% CI 9.9-11.7) than in the de novo group at 7.3 m (95% CI 7.0-7.7, p < 0.001). We did not observe a significant difference in OS based on when patients recurred after surgery: 10.0 m (95% CI 8.7-11) within six months of surgery versus 11.6 m (95% CI 10-12, p = 0.256) greater than six months from surgery.Conclusions: These data support the inclusion of patients with recurrent PDAC in clinical trials for advanced disease, including those who develop recurrent disease within six months of surgery. Due to observed differences in survival, randomization should be stratified by disease presentation (recurrent vs de novo). [ABSTRACT FROM AUTHOR]

Aims: To provide real‐world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) therapy. However, real‐world data on the addition of BI to GLP‐1RA therapy are limited. Materials and Methods: We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real‐world impact of adding the second‐generation BI analogue insulin glargine 300 U/mL (Gla‐300) to GLP‐1RA therapy. Insulin‐naïve PWD2 receiving GLP‐1RAs who also received Gla‐300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla‐300. Results: The mean (standard deviation [SD]) age of participants (N = 271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (−0.97 [SD 1.60]%; P < 0.0001) after addition of Gla‐300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla‐300 (HbA1c <7.0%: 4.80% vs. 22.14%, P < 0.0001; HbA1c <8.0%: 19.56% vs. 51.29%, P < 0.0001). The incidence of overall (8.49% vs. 9.59%; P = 0.513) and inpatient/emergency department (ED)‐associated hypoglycaemia (0.37% vs. 0.74%; P = 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P = 0.170) and inpatient/ED‐associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P = 0.466) were similar before and after addition of Gla‐300. Conclusions: In US real‐world clinical practice, adding Gla‐300 to GLP‐1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla‐300 to GLP‐1RA therapy is warranted. [ABSTRACT FROM AUTHOR]

In England, not all cancer drugs are routinely funded; new medicines are first appraised by the National Institute for Health and Care Excellence. Funding can be temporarily given through the Cancer Drugs Fund while further information is collected. The Systemic Anti-Cancer Therapy (SACT) dataset collects information on all patients receiving chemotherapy in England. To date, little has been published, despite concerns that real-world effectiveness of medicines may be inferior to that seen in clinical trials. The aim of the present study was to establish the feasibility of using our local copy of routinely collected SACT data for the evaluation of outcomes, using the data within the context of gastrointestinal cancers. We used our local SACT dataset submissions from three National Health Service trusts, with a reproducible method of data linkage, to undertake a cohort analysis of treatment duration and overall survival for cetuximab, panitumumab, trifluridine/tipiracil (all three in colorectal cancer), sorafenib (in hepatocellular cancer) and nab-paclitaxel (nanoparticle albumin-bound paclitaxel) with gemcitabine (in pancreatic cancer) for all patients treated from May 2016 to March 2021. In our population, epidermal growth factor receptor inhibitors and trifluridine/tipiracil and sorafenib performed similarly to expected but nab-paclitaxel with gemcitabine in pancreatic cancer seemed to be no better than gemcitabine alone, when given within the current funding arrangements in England. Our results support the publication of national outcome data. If these results are confirmed on a larger cohort, it would support the reappraisal of certain drugs and provide further evidence to clinicians and patients when deciding the best treatment. • This study used local data and a simple IT system to analyse real-world outcomes. • Cetuxumab, panitumumab, sorafenib and trifluridine/tipiracil outcomes matched trials. • nab-paclitaxel in pancreatic cancer had poorer outcomes than expected. [ABSTRACT FROM AUTHOR]

Background: Real-world data are limited for patients with brain metastases secondary to metastatic breast cancer (MBC) and treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). This study describes real-world outcomes in patients with hormone receptor-positive, human epidermal growth factor 2-negative (HR+/HER2-) MBC with brain metastases diagnosis before abemaciclib initiation., Patients and Methods: A nationwide electronic health record-derived de-identified MBC database (January 2011-December 2021) was assessed retrospectively. Patients with HR+/HER2- MBC who were treated with abemaciclib (monotherapy or in combination) following diagnosis of brain metastases were included. Real-world best response reflected clinician-documented response assessment of the brain imaging (intracranial) and change in disease burden following radiographic imaging (extracranial); these were reported descriptively. Time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (rwOS) were assessed using Kaplan-Meier methods from abemaciclib initiation (index date)., Results: Among 82 included patients (mean age 57.0 years; 98.8% female), 22.0% and 19.5% received CDK4/6i and chemotherapy before abemaciclib initiation, respectively, and the majority (80.5%) received radiation/local surgery to the brain before abemaciclib initiation. Patients mostly received abemaciclib as monotherapy (n = 6) or in combination with endocrine therapy (n = 68). Median TTD was 7.1 (95% CI 4.6-11.3) months, rwPFS was 9.2 (95% CI 6.0-11.6) months, and rwOS was 20.8 (95% CI 13.9-26.0) months. Intracranial and extracranial objective response rates, as determined by treating physicians, were 45.1% (n = 23/51) and 56.7% (n = 34/60), respectively. Intracranial and extracranial clinical benefit rates were 62.7% (n = 32/51) and 70.0% (n = 42/60), respectively., Conclusion: In this real-world study of patients diagnosed with brain metastases and initiating abemaciclib, most patients received radiation/local surgery to the brain before abemaciclib initiation. Although the outcomes in this real-world study are encouraging, it is unclear if the benefit was due to local therapy, abemaciclib, or the combination, and causality cannot be inferred. Further prospective clinical studies are needed to confirm the clinical benefit of this approach., (© The Author(s) 2024. Published by Oxford University Press.)

Simple Summary: Most adult patients with acute myeloid leukemia (AML) relapse after achieving complete remission with chemotherapy; however, there is no standard second-line (salvage) treatment. We retrospectively investigated 404 patients aged ≥18 years with relapsed/refractory (R/R) AML with an FMS-like tyrosine kinase 3 (FLT3) mutation, treated at a PETHEMA (NCT02607059) site between 1998 and 2018. Patients received salvage treatment with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care (n = 80). Complete remission was achieved by 48% of patients who received intensive therapy vs. 19% with non-intensive therapy. Intensive/non-intensive therapy prolonged overall survival significantly compared with supportive therapy. Of evaluable patients, 22% received an allogeneic stem-cell transplant after complete remission. The majority of patients with FLT3-mutated R/R AML received intensive salvage therapy, with the best outcomes being obtained when intensive salvage treatment was combined with stem-cell transplant. This retrospective study investigated outcomes of 404 patients with relapsed/refractory (R/R) FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) enrolled in the PETHEMA registry, pre-approval of tyrosine kinase inhibitors. Most patients (63%) had received first-line intensive therapy with 3 + 7. Subsequently, patients received salvage with intensive therapy (n = 261), non-intensive therapy (n = 63) or supportive care only (n = 80). Active salvage therapy (i.e., intensive or non-intensive therapy) resulted in a complete remission (CR) or CR without hematological recovery (CRi) rate of 42%. More patients achieved a CR/CRi with intensive (48%) compared with non-intensive (19%) salvage therapy (p < 0.001). In the overall population, median overall survival (OS) was 5.5 months; 1- and 5-year OS rates were 25% and 7%. OS was significantly (p < 0.001) prolonged with intensive or non-intensive salvage therapy compared with supportive therapy, and in those achieving CR/CRi versus no responders. Of 280 evaluable patients, 61 (22%) had an allogeneic stem-cell transplant after they had achieved CR/CRi. In conclusion, in this large cohort study, salvage treatment approaches for patients with FLT3-ITD mutated R/R AML were heterogeneous. Median OS was poor with both non-intensive and intensive salvage therapy, with best long-term outcomes obtained in patients who achieved CR/CRi and subsequently underwent allogeneic stem-cell transplant. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utilization and outcomes of PD-1-directed immunotherapy (PD-1 IMT) for advanced hepatocellular carcinoma. Methods: Patients with advanced hepatocellular carcinoma receiving systemic therapy and PD-1 IMT (nivolumab/pembrolizumab) were included from the Flatiron database. Overall survival (OS) was evaluated using multivariable Cox models with the following subgroup analyses: patients with data on clinical performance and liver function and patients receiving tyrosine kinase inhibitors. Results: n = 1770 patients were included (PD-1 IMT 19.3%). Overall, PD-1 IMT was associated with longer OS (hazard ratio [HR]: 0.57). This effect was robust across both subgroup analyses with HR: 0.72 (subgroup 1) and HR: 0.57 (subgroup 2). Conclusions: PD-1 IMT is increasingly used in clinical practice and associated with an OS benefit. [ABSTRACT FROM AUTHOR]

Purpose: To examine the 16-week outcomes of switching to brolucizumab in eyes with neovascular age-related macular degeneration (nAMD) refractory to aflibercept. Study design: Retrospective observational study. Methods: Data of eyes with nAMD who switched to brolucizumab because of resistance to aflibercept were collected. The best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative status on optical coherence tomography were analyzed. Results: A total of 48 eyes of 48 patients were reviewed. At 4 to 7 weeks after switching, BCVA changed from 0.26 ± 0.19 to 0.25 ± 0.21 (not significant; P = 0.95), but CRT significantly decreased from 298.9 ± 108.4 µm to 241.9 ± 92.5 µm (P < 0.001) and CCT from 182.6 ± 89.3 µm to 169.7 ± 82.6 µm (P < 0.001). Of the 23 eyes refractory to monthly aflibercept injections, 12 (52.2%) achieved a dry macula, and 8 (34.8%) reduced exudative changes at 1 month. At 16 weeks, 31 eyes (64.6%) achieved the treatment interval ≥ 8 weeks. Two patients (4.2%) dropped out, 7 eyes (14.6%) developed intraocular inflammation (IOI), and 8 eyes (16.7%) switched back to aflibercept because of the failure to extend the treatment interval ≥ 8 weeks. Conclusion: Switching to brolucizumab in eyes refractory to aflibercept conferred favorable outcomes in controlling exudative changes. However, IOI and the regulation of the treatment interval to at least 8 weeks during the maintenance phase disrupted the continuation of brolucizumab treatment. [ABSTRACT FROM AUTHOR]

Introduction: To date, there are limited real-world studies published on the use of infliximab-dyyb, a biosimilar to reference product (RP) infliximab approved for the treatment of moderate to severe inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in North America. This study examined utilization patterns and the effects of infliximab-dyyb on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use (HCRU) in IBD patients in a real-world setting. Methods: In this prospective, observational study, adult IBD patients in the US and Canada were recruited to initiate treatment with infliximab-dyyb and followed for 12 months. Patients included biologic-naïve users of infliximab-dyyb and patients switching from RP infliximab or other biologics to infliximab-dyyb. Partial Mayo (pMAYO) and Harvey Bradshaw Index (HBI) scores measured clinical outcomes for the UC and CD cohorts, respectively. Key PRO measures included the SIBDQ, EQ-VAS, and psychological outcomes. In addition, work productivity, HCRU, and adverse events (AEs) were assessed. Results: A total of 67 CD and 48 UC patients were enrolled (51% female; mean age 44 years; 87% Caucasian; mean BMI 27.9). Thirty-nine patients were biologic-naïve, 57 switched from RP infliximab, and 19 switched from other biologics. Among UC biologic-naïve users, pMAYO decreased from 5.67 to 1.09 (p < 0.0001) and the remission rate increased from 5.6 to 90.9% (p = 0.0015). For UC patients switching from RP infliximab, pMAYO decreased from 1.38 to 0.29 (p = 0.0103). For CD biologic-naïve users, HBI scores and remission rates did not significantly change. The scores on all the PROs significantly improved from baseline to 12 months. A total of 22 AEs occurred consistent with the known AE profile for infliximab. Conclusions: Clinical outcomes among biologic-naïve users of infliximab-dyyb improved for UC and were maintained for CD patients. Biologic-naïve users of infliximab-dyyb showed significant improvements in PROs. Patients switching from RP infliximab to infliximab-dyyb maintained their clinical outcomes and PROs. Trial Registration: ClinicalTrials.gov Registration Number: NCT03801928 (February 23, 2018). [ABSTRACT FROM AUTHOR]

Abstract Background The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. Methods Electronic prescribing records of treatment-naive patients starting first-line (1 L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response. Results In all, 1003 patients were evaluated (median age, 68 years [range, 28–93 years]; 53.9% male). Use of 1 L IO monotherapy (0–25.9%) and targeted therapy (11.8–15.9%) increased during the study period, but chemotherapy remained the most common 1 L treatment at all time points (88.2–58.2%). Median OS was 9.5 months (95% CI, 8.8–10.7 months) for all patients, 8.1 months (95% CI, 7.4–8.9 months) with chemotherapy, 14.0 months (95% CI, 10.7–20.6 months) with IO monotherapy, and 20.2 months (95% CI, 16.0–30.5 months) with targeted therapy. In the 28.6% of patients who received second-line treatment, IO monotherapy was the most common drug class (used in 51.6%). Conclusions Although use of 1 L IO monotherapy for aNSCLC increased in the United Kingdom during the study period, most patients received 1 L chemotherapy. An OS benefit for first-line IO monotherapy vs chemotherapy was observed but was numerically smaller than that reported in clinical trials. Targeted therapy was associated with the longest OS, highlighting the need for improved treatment options for tumors lacking targetable mutations.

Introduction: Phase III clinical trials of dexamethasone intravitreal implant for diabetic macular oedema (DMO) have reported significant improvements in visual acuity (VA). Studies evaluating the treatment of DMO in routine clinical practice provide data to identify areas that need improvement. This study evaluated 12-month treatment outcomes of dexamethasone implant for DMO in routine clinical practice. Methods: Retrospective data analysis of eyes that started dexamethasone implant for DMO from 1 June 2013 to 30 April 2019 in routine clinical practice tracked in the Fight Retinal Blindness! Registry. Results: Of the 4282 eyes (2518 patients) that started DMO treatment in the specified period, 267 (6%) eyes (204 patients) received 454 dexamethasone implant injections. Two-fifths (106 eyes) had received prior treatment for DMO. The mean (95% confidence interval [CI]) VA change at 12 months was 1.8 (− 0.5, 4.2) letters from the mean (standard deviation [SD]) VA of 56.5 (19.8) letters at baseline, with 41% eyes achieving at least 20/40. The mean (95% CI) change in central subfield thickness over 1 year was − 79 (− 104, − 54) µm from a mean (SD) of 459 (120) µm at baseline. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 2 (1, 2) dexamethasone implants. One-tenth of phakic eyes received cataract surgery while 2% had a pressure response requiring anti-glaucoma medications. Conclusions: One-year treatment outcomes of dexamethasone intravitreal implant for DMO in routine clinical practice were inferior to those in the clinical trials perhaps because of fewer treatments in clinical practice. [ABSTRACT FROM AUTHOR]

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014–2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population. [ABSTRACT FROM AUTHOR]

Objective: We sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) or reoperative surgical aortic valve replacement (redo-SAVR) in the Netherlands. Methods: Patients who had undergone ViV-TAVI or redo-SAVR for a degenerated biological aortic valve prosthesis in the Netherlands between January 2014 and December 2018 were eligible for this retrospective study. Patients with a prior homograft, active endocarditis or mechanical aortic valve prosthesis were excluded. Patients were matched using the propensity score. The primary endpoint was a composite of 30-day all-cause mortality and in-hospital postoperative stroke. Secondary endpoints were all-cause mortality at different time points, in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year. Baseline characteristics and outcome data were collected from the Netherlands Heart Registration. Results: From 16 cardiac centres, 653 patients were included in the study (374 ViV-TAVI and 279 redo-SAVR). European System for Cardiac Operative Risk Evaluation I (EuroSCORE I) was higher in ViV-TAVI patients (19.4, interquartile range (IQR) 13.3–27.9 vs 13.8, IQR 8.3–21.9, p < 0.01). After propensity score matching, 165 patients were matched with acceptable covariate balance. In the matched cohorts, the primary endpoint was not significantly different for ViV-TAVI and redo-SAVR patients (odds ratio 1.30, 95% confidence interval 0.57–3.02). Procedural, 30-day and 1‑year all-cause mortality rates, incidence of in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year were also similar between cohorts. Conclusion: Patients with degenerated aortic bioprostheses treated with ViV-TAVI or redo-SAVR have similar mortality and morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Hyperkalemia is often managed in the emergency department (ED) and it is important to understand how ED management and post-discharge outcomes vary by hyperkalemia severity. This study was conducted to characterize ED management and post-discharge outcomes across hyperkalemia severities. Methods: Adults with an ED visit with hyperkalemia (at least one serum potassium lab measure above 5.0 mEq/L) were selected from US electronic medical record data (2012–2018). Patient characteristics, potassium levels, treatments, and monitoring prior to and during the ED visit were compared by hyperkalemia severity (mild [> 5.0–5.5 mEq/L], moderate [> 5.5–6.0], severe [> 6.0]) using unadjusted analyses. Death, immediate inpatient admission, 30-day hyperkalemia recurrence, and 30-day inpatient admission were also assessed by severity. Results: Of 6222 patients included, 4432 (71.2%) had mild hyperkalemia, 1085 (17.4%) had moderate, and 705 (11.3%) had severe hyperkalemia. Chronic kidney disease (39.9–50.1%) and heart failure (21.6–24.3%) were common. In the ED, electrocardiograms (mild, 56.5%; moderate, 69.6%; severe, 81.0%) and patients with at least two potassium laboratory values increased with severity (15.0%; 40.4%; 75.5%). Among patients with at least two potassium laboratory values, over half of patients (60.4%) had potassium levels ≤ 5.0 mEq/L prior to discharge. Use of potassium-binding treatments (sodium polystyrene sulfonate: mild = 4.1%; moderate = 17.1%; severe = 27.4%), temporizing agents (5.6%; 15.5%; 31.6%), or dialysis (0.4%; 0.8%; 3.0%) increased with severity; treatment at discharge was not common. Death (1.1%; 3.7%; 10.6%), immediate admission to inpatient care (5.8%; 8.7%; 12.7%), 30-day hyperkalemia recurrence (2.9%; 19.0%; 32.5%), 30-day inpatient admission with hyperkalemia (6.5%; 7.9%; 9.3%) also increased with severity. Conclusion: Patients with moderate and severe hyperkalemia experienced elevated risk of hyperkalemia recurrence and hyperkalemia-related inpatient readmission following discharge from the ED from a descriptive analysis. Future research to assess strategies to reduce hyperkalemia recurrence and inpatient admission in this patient population would be beneficial. [ABSTRACT FROM AUTHOR]

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that affects older adults with frequent comorbidities, making real-world treatment decisions challenging. This study compares the overall survival (OS) of patients with MPM by physician’s choice of first-line (1L) platinum chemotherapy (PC), second-line (2L) immunotherapy versus chemotherapy, and by receipt of maintenance therapy (MT). Methods: The study included patients diagnosed with advanced MPM in the Flatiron Health electronic health record–derived database who initiated PC with pemetrexed in the 1L setting between 2011 and 2019. Patients in the 2L therapy analysis received single-agent chemotherapy versus immunotherapy after the progression of disease from our 1L cohort. Patients in the MT cohort were identified on the basis of continued receipt of pemetrexed with or without bevacizumab after dropping PC at prespecified intervals. The OS of patients by choice of 1L PC, 2L immunotherapy versus chemotherapy, and receipt of MT was summarized by means of Kaplan-Meier survival estimates and compared in the context of propensity score matching weighted analyses. Results: In propensity score matching weighting analysis from 2065 patients with MPM, there was no evidence of an OS difference by choice of 1L PC (hazard ratio [HR] = 1.08, 95% confidence interval [CI]: 0.89–1.31, p = 0.43), suggestive evidence of an OS difference by choice of 2L immunotherapy versus chemotherapy (HR = 0.68, 95% CI: 0.42–1.08; p = 0.10), and no evidence of an OS difference by receipt of MT (HR = 0.92, 95% CI: 0.72–1.16, p = 0.46). Conclusions: Using real-world, propensity score–matched weighted analysis of MPM, we found there was no difference in OS by choice of 1L PC, 2L immunotherapy or chemotherapy, or by receipt of MT.

Introduction: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first‐of‐its‐kind, pan‐India, prospective, observational study aimed to evaluate real‐world patterns and management of T2DM over 3 years. Methods: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti‐diabetic agents) were enrolled. The first‐year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non‐metropolitan cities are reported here. Results: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non‐ metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: −0.5% vs. −0.5%; p =.8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p <.0001) higher in non‐metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti‐diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase‐IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p <.0001) higher in the insulin vs. the insulin‐naïve subgroups; in the insulin‐naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs. Conclusions: First‐year trends of the LANDMARC study offer insights into real‐world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM. [ABSTRACT FROM AUTHOR]

Abstract Introduction Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first‐of‐its‐kind, pan‐India, prospective, observational study aimed to evaluate real‐world patterns and management of T2DM over 3 years. Methods Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti‐diabetic agents) were enrolled. The first‐year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non‐metropolitan cities are reported here. Results Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c 3 vs. ≤3 OADs. Conclusions First‐year trends of the LANDMARC study offer insights into real‐world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM.

Fidaxomicin, a macrocyclic antibiotic, selectively kills Clostridioides difficile and reduces C. difficile infection (CDI) recurrence compared with vancomycin, but some studies and guidelines report fidaxomicin as being less cost-effective. The aim of this study was to compare the cost-effectiveness and budget impact of fidaxomicin versus vancomycin or metronidazole for treating CDI in a real-world UK setting. Data were retrospectively collected from medical records of 86 patients with CDI treated with vancomycin or metronidazole at a single UK hospital between April 2011 and March 2012, and prospectively from 62 patients with CDI treated with fidaxomicin between August 2012 and July 2013. CDI cases were matched by age, financial year, and healthcare resource use to control cases. CDI recurrence rates were lower with fidaxomicin (6.5%) than vancomycin/metronidazole (19.8%). An estimated 12 additional recurrent CDIs were prevented with fidaxomicin treatment. Patients with CDI had significantly higher healthcare costs than those without CDI, with a mean excess spend of GBP 10,748 and GBP 17,451 per patient in the fidaxomicin (p = 0.015) and vancomycin/metronidazole cohorts (p < 0.001), respectively. A second CDI was associated with mean excess costs of GBP 8373 and GBP 20,249 per patient in the fidaxomicin and vancomycin/metronidazole cohorts, respectively. Despite higher fidaxomicin drug costs, overall cost savings were estimated at GBP 140,292 (GBP 2125 per CDI). In this real-world study, first-line CDI treatment with fidaxomicin reduced healthcare costs versus vancomycin/metronidazole, consistent with previous studies.

Objective: Mitral valve repair (MVr) has become the standard therapy for degenerative mitral regurgitation (DMR), but real-world late mortality, reintervention, and readmission data are lacking. This study estimates MVr outcomes for DMR to 3 years in the Medicare fee-for-service population., Methods: There were 4,219 DMR patients older than 65 years undergoing MVr within the Medicare 100% standard analytic file from October 2015 to December 2018 who were evaluated. Outcomes were analyzed for isolated MVr patients ( n = 2,433) and patients undergoing MVr with certain concomitant procedures: MVr + tricuspid valve surgery (TVS; n = 619), MVr + cardiac ablation (CA; n = 540), and MVr + left atrial appendage closure ( n = 627). Outcomes over a 3-year period included all-cause mortality, reintervention, rehospitalization, and common complications. All outcomes were modeled with adjustments for patient demographics and comorbid conditions., Results: The average age for all patients was 71.9 ± 5.2 years. Adjusted all-cause mortality and MV reintervention (surgery or transcatheter) at 3 years for the primary cohort of isolated MVr was 3.5% and 1.6%, respectively. Directionally higher mortality at 3 years was observed in patients with concomitant TVS or CA. All-cause readmission and cardiac readmission for isolated MVr was 37.0% and 14.1%, with the highest rates for those with concomitant TVS or CA. Acute kidney injury and stroke/transient ischemic attack were the most common adverse events over 3 years for all patients., Conclusions: The 3-year mortality and reintervention rates in Medicare patients undergoing degenerative MVr are low. Those undergoing concomitant TVS or CA had directionally higher mortality and cardiac readmission rates. These results help refine outcome benchmarks as new transcatheter MVr procedures continue to emerge., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Thourani reports receiving grants from Edwards Lifesciences; receiving payment or honoraria for lectures, presentations, speakers bureau, manuscript writing, or educational events from Edwards Lifesciences; and being a consultant and conducting research for Abbott Vascular, Artivion, AtriCure, Boston Scientific, Edwards Lifesciences, JenaValve, and Medtronic. Dr Vemulapalli has received grants/contracts from the American College of Cardiology, Society of Thoracic Surgeons, Cytokinetics, Abbott Vascular, National Institutes of Health (R01 and SBIR), and Boston Scientific and has received consulting fees/been on the advisory board with Janssen, American College of Physicians, HeartFlow, and Edwards LifeSciences. Dr Gammie is a consultant for Edwards Lifesciences and founder of Protaryx Medical and of Marlin Medical. Dr Nguyen has received speaker honoraria from Edwards Lifesciences, CryoLife, and Abbott.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177 Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177 Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177 Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177 Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177 Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177 Lu-DOTATATE treatment., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: The objective of this study was to describe the real-world use and effectiveness of dolutegravir-based regimens (DBRs) in routine clinical practice in the United Kingdom. Methods: Retrospective analysis was conducted using data from four National Health Service trusts using Climate-HIV, an electronic case record system. Eligible patients were aged ≥18 years with HIV-1 infection who were prescribed a DBR from December 2012 to March 2018. Outcome measurements were accessed at DBR initiation and at weeks 24, 48 and 96 and the last recorded visit up to the extraction date (last measurement). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48. Results: The study cohort included 934 patients; 337 (36%) were female, 414 (47%) were white and 717 (77%) were treatment experienced (TE). The Kaplan–Meier estimated probability of achieving HIV-1 RNA <50 copies/mL at 48 weeks was 96% for treatment-naive (TN) patients and 86% for TE patients. Median times to viral suppression (<50 copies/mL) were 49 and 57 days for TN and TE patients with detectable baseline viral load, respectively, according to Kaplan–Meier analysis. Median follow-up time was 377 days (interquartile range: 131–683). At last measurement, 87% (809/934) of patients remained on a DBR; among those patients, 681 (84%) had HIV-1 RNA <50 copies/mL. Conclusions: High levels of virologic suppression and low rates of discontinuation of DBRs were seen in a large, diverse, UK-based population with HIV-1 infection. These findings are broadly consistent with efficacy data from phase III studies. [ABSTRACT FROM AUTHOR]