Pneumatic retinopexy for primary rhegmatogenous retinal detachment: from a clinical trial to the real-life experience.

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.

A real-world multicentre evaluation of atezolizumab plus platinum-etoposide chemotherapy as first-line treatment in patients with extensive-stage small cell lung cancer in Italy.

INTRODUCTION: The aim of this study was to analyze real-life data from a cohort of adult patients receiving atezolizumab in combination with carboplatin and etoposide for first-line treatment of ES-SCLC, in order to assess relative dose intensity (RDI), time-to-treatment discontinuation (TTD), time-to-treatment failure (TTF), progression-free survival (PFS), overall survival (OS) of treatments as well as the correlation between these outcomes. METHODS: An observational retrospective study was conducted. All patients treated with atezolizumab combined with carboplatin and etoposide for first-line treatment of ES-SCLC were included. Median TTD, TTF, PFS and OS were calculated in our cohort of patient by the Kaplan Meier method. RESULTS: The curves obtained with the Kaplan Meier method of TTF and TTD are substantially similar, indicating a good concordance of the information extracted by the two different data sources. This tendency was confirmed also when the TTD versus PFS curves were compared. The median OS registered was 11.8 months. Patients with no liver metastases showed a longer median time of OS than patients with liver metastases. The mean value of RDI for the entire cohort was 87.4%. CONCLUSIONS: Our study showed that TTD, calculated from the administration data is a useful proxy of TTF as registered in the clinical chart. TTD is a real-world outcome that can be used to demonstrate the efficacy of drugs used for administered therapies. It can be used as an end point for RWE studies, where the evaluation is less structured and standardized.

Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma.

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.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

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.

Real-world outcomes of adult patients with acute lymphoblastic leukemia treated with a modified CALGB 10102 regimen.

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).

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

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.

Real-world outcomes with fedratinib therapy in patients who discontinued ruxolitinib for primary myelofibrosis.

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.

Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

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.

What is this article about? 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. What were the results? 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. What do the results of the study mean? 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.

Real-world outcomes of low-dose atropine therapy on myopia progression in an Australian cohort during the COVID-19 pandemic.

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.

Treatment outcomes in recurrent versus de novo metastatic pancreatic adenocarcinoma: a real world study.

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).

Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in people with type 2 diabetes: The DELIVER-G study.

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.

PD-1 targeted immunotherapy for advanced hepatocellular carcinoma: current utilization and outcomes in the USA.

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.

PD-1-directed immunotherapy (PD-1 IMT) is increasingly used for the treatment of advanced hepatocellular carcinoma in the USA. Patients receiving PD-1 IMT demonstrate a favorable overall survival compared with those without PD-1 IMT treatment.

Practice patterns and outcomes for triple-class exposed patients with relapsed/refractory multiple myeloma in Japan.

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.

Treatment options are limited for patients with multiple myeloma (MM) in Japan who have received the 3 classes of drugs known as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, and are considered to be 'triple-class exposed' (TCE). The objective of this study was to understand the characteristics of this patient population and the treatments they received after becoming TCE. The study evaluated healthcare resources and costs and considered whether patients had received stem cell transplant as their first treatment, where cells that may differentiate into blood cells are administered. This study analyzed a database of anonymous patients' medical records collected from April 2008 through April 2021 in Japan. A total of 216 patients were included, of whom 194 never received stem cell transplantation. Patients who received treatment after being considered TCE received that first treatment for a median of 2 months. All patients who received treatment after TCE had a median overall survival of 15.8 months meaning half the patients were still alive after receiving treatment at 15.8 months. Patients who did not have a stem cell transplant after diagnosis had a median overall survival of 17.4 months. Healthcare resources were similar between groups, except those who did not have stem cell transplantation after diagnosis needed more medications. Both groups had total healthcare costs of ¥1.3 million per patient per month. These findings support the need for new treatments and future studies to understand how new treatments would help TCE relapsed or refractory multiple myeloma patients in Japan.

Report on outcomes of valve-in-valve transcatheter aortic valve implantation and redo surgical aortic valve replacement in the Netherlands.

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 1­year 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.

Cancer clinical trial vs real-world outcomes for standard of care first-line treatment in the advanced disease setting.

Clinical trials have strict eligibility criteria, potentially limiting external validity. However, while often discussed this has seldom been explored, particularly across cancer types and at variable time frames posttrial completion. We examined comprehensive registry data (January 2014 to June 2019) for standard first-line treatments for metastatic colorectal cancer (CRC), advanced pancreatic cancer (PC), metastatic HER2-amplified breast cancer (BC) and castrate-resistant prostate cancer (CaP). Registry patient characteristics and outcomes were compared to the practice-changing trial. Registry patients were older than the matched trial cohort by a median of 2-6 years (all P = <.01) for the CRC, BC and PC cohorts. The proportion of Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 patients was lower for CRC (94.1% vs 99.2%, P = .001) and BC (94.9% vs 99.3%, P = .001). Progression-free survival (PFS) for registry patients was similar to the trial patients or significantly longer (CaP, Hazard Ratio [HR] = 0.65, P = <.001). Overall survival (OS) was also similar or significantly longer (CaP, HR 0.49, P = <.001). In conclusion, despite real-world patients sometimes being older or having inferior PS to trial cohorts, the survival outcomes achieved were consistently equal or superior to those reported for the same treatment in the trial. We suggest that this is potentially due to optimised use of each treatment over time, improved multidisciplinary care and increased postprogression options. We can reassure clinicians and patients that outcomes matching or exceeding those reported in trials are possible. The potential for survival gains over time should routinely be factored into future trial statistical plans.

Metastatic melanoma patient outcomes since introduction of immune checkpoint inhibitors in England between 2014 and 2018.

Immune checkpoint inhibitors (CPIs) have radically changed outcomes for patients diagnosed with metastatic melanoma globally in the last 10 years, based on evidence of overall survival (OS) benefits generated from international randomised controlled trials (RCTs). Since RCTs do not always reflect real-world prescribing, we interrogated established national databases to track prescribing of CPIs approved for first line treatment of metastatic melanoma patients in England since 2014 and determined patient outcomes associated with OS, as well as treatment-related toxicity. Between April 2014 and March 2018, 5465 melanoma patients were diagnosed and treated with systemic anticancer therapy (SACT), 2322 of which received first-line CPIs. There was good 3-year OS concordance with RCT outcomes for ipilimumab (32%), ipinivo (56%) and nivolumab (51%), but OS was lower than expected for pembrolizumab (40%). Comparing patients prescribed ipinivo with those prescribed pembrolizumab, ipinivo-treated patients were younger (88% vs 49% patients <70 years, P < .001) and fitter (60% vs 38% patients with Eastern Cooperative Oncology Group [ECOG] performance status 0, P < .0001). Emergency hospital admission rates from the earliest and last treatment dates were higher for patients prescribed ipinivo (37% and 55%) compared to those prescribed pembrolizumab (17% and 29%). The 30-day mortality rates favoured ipinivo patients (3.8% ipinivo, 9.1% pembrolizumab, P < .0001) and likely reflected marked differences in median treatment durations: 63 (range 7-440) days for ipinivo and 192 (range 5-943) days for pembrolizumab. The dominant treatment-related condition linked to hospital admission was colitis, recorded for 25% of patients prescribed ipinivo compared to 4% of patients prescribed pembrolizumab. Our population data has demonstrated that RCT outcomes can be achieved in routine care settings with careful patient selection.

Real-World Clinical Outcomes in Patients with Locally Advanced or Metastatic Merkel Cell Carcinoma Treated in U.S. Oncology Clinical Practices: Results from SPEAR-Merkel.

BACKGROUND: Immunotherapy (IO) has been associated with improved outcomes in patients with locally advanced Merkel cell carcinoma (laMCC) and metastatic Merkel cell carcinoma (mMCC). The primary objective of SPEAR-Merkel was to explore treatment patterns, clinical outcomes, and health care resource utilization (HCRU) in patients with laMCC or mMCC initiating first-line (1L) treatment with avelumab, non-avelumab IO, or chemotherapy in a U.S. community oncology setting. METHODS: Adult patients with laMCC or mMCC initiating 1L avelumab, non-avelumab IO, or chemotherapy from January 1, 2015, to March 31, 2019, were identified from the U.S. Oncology Network electronic health care record database and followed up through September 30, 2019. Baseline characteristics and HCRU were analyzed descriptively, including physician-stated overall response rate in the real-world clinical setting. Kaplan-Meier methods were used to measure duration of response, real-world progression-free survival (rwPFS), and overall survival (OS). RESULTS: Among the overall population (n = 94), 28 received 1L avelumab (9 laMCC, 19 mMCC), 26 received 1L non-avelumab IO (8 laMCC, 18 mMCC), and 40 received 1L chemotherapy (10 laMCC, 30 mMCC). The real-world overall response rate was 64.3%, 61.5%, and 42.5%, respectively. From 1L treatment initiation, median rwPFS was 11.4, 8.1, and 6.1 months, and median OS was 20.2 months, not reached, and 14.7 months for the respective cohorts. CONCLUSION: SPEAR-Merkel showed that patients with laMCC or mMCC treated with IO had improved outcomes compared with chemotherapy in clinical practice. The study provides insight on utilization and clinical outcomes associated with newer, more innovative therapies in clinical practice, which may help clinicians understand the variety of newer treatment options for both laMCC and mMCC. IMPLICATIONS FOR PRACTICE: To the authors' knowledge, SPEAR-Merkel is the first study to evaluate real-world clinical outcomes in patients with locally advanced Merkel cell carcinoma (laMCC) and metastatic Merkel cell carcinoma (mMCC) receiving first-line (1L) avelumab, non-avelumab immuno-oncology therapies, or chemotherapy in a real-world setting. SPEAR-Merkel showed clinical benefit for immuno-oncology therapies compared with chemotherapy. The study provides insight on uses and clinical outcomes associated with innovative therapies in clinical practice, which may help clinicians understand the variety of newer treatment options for both laMCC and mMCC. The study is of particular importance as it shows that chemotherapy is still being used as 1L treatment despite its inferior clinical and safety profile.

Retrospective analysis of real-world treatment patterns and clinical outcomes in patients with advanced non-small cell lung cancer starting first-line systemic therapy in the United Kingdom.

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.

Treatment patterns in patients with metastatic non-small-cell lung cancer in the era of immunotherapy.

Background: Chemotherapy (CT) alone was previously standard first-line (1L) therapy for metastatic non-small-cell lung cancer (NSCLC) but alternative treatments, including immunotherapy (I-O), are now available. Patients & methods: In this retrospective study, adults with stage IV NSCLC who initiated 1L treatment between 1 August 2018 and 31 December 2019 and had ≥2 visits were identified in the Flatiron database. Patients were followed up until 30 June 2020. Baseline characteristics and treatment patterns were described by treatment group: CT, I-O + CT, I-O monotherapy and other. Results: Approximately 20% of patients received 1L CT in the 2018-2019 timeframe studied; these patients tended to have squamous histology and low (≤49%) programmed death ligand-1 expression. Conclusion: A proportion of patients with metastatic NSCLC still receive 1L CT despite the availability and widespread use of I-O therapies.

The use of ecological momentary assessment to evaluate real-world aided outcomes with children.

BACKGROUND: Ecological momentary assessment (EMA) methods allow for real-time, real-world survey data collection. Studies with adults have reported EMA as a feasible and valid tool in the measurement of real-world listening experience. Research is needed to investigate the use of EMA with children who wear hearing aids. OBJECTIVES: This study explored the implementation of EMA with children using a single-blinded repeated measures design to evaluate real-world aided outcome. METHODS: Twenty-nine children, aged 7-17, used manual program switching to access hearing aid programs, fitted according to Desired Sensation Level (DSL) version 5.0 child quiet and noise prescriptive targets. Aided outcome was measured using participant-triggered twice-daily EMA entries, across listening situations and hearing dimensions. RESULTS: Adherence to the EMA protocol by the children was high (82.4% compliance rate). Speech loudness, understanding and preference results were found to relate to both the hearing aid program and the listening situation. Aided outcomes related to prescription-based noise management were found to be highest in noisy situations. CONCLUSIONS: Mobile device-based EMA methods can be used to inform daily life listening experience with children. Prescription-based noise management was found to decrease perceived loudness in noisy, non-school environments; this should be evaluated in combination with hearing aid noise reductions features.