Real-world utilization of lenvatinib and pembrolizumab combination therapy for the treatment of endometrial cancer in the USA.

Aim: Describe treatment and dosing patterns of lenvatinib and pembrolizumab combination therapy (lenva+pembro) among endometrial cancer (EC) patients in US clinical practice. Materials & methods: Retrospective cohort study among adults with EC initiating lenva+pembro in second line (2L) or third line and later (≥3L) between 17 September 2019 and 30 June 2021. Results: 110 patients initiated lenva+pembro in 2L and 135 patients in ≥3L. Majority of patients initiated lenva+pembro at label-recommended starting doses/interval. Less than half changed lenvatinib dose over time. At median follow-up of 7.3 and 8.7 months, median (95% CI) duration of therapy was 5.1 (4.7-6.1) and 5.8 (4.2-7.3) months for patients in 2L and ≥3L, respectively. Conclusion: Lenva+pembro was mostly initiated at label-recommended dose.

This study looked at details of lenvatinib and pembrolizumab combination treatment among patients with endometrial cancer (EC) in the USA. Specifically, these patients had received prior chemotherapy or hormone therapy before starting lenvatinib and pembrolizumab. Most patients started lenvatinib and pembrolizumab at the dose recommended by the product label and received the next pembrolizumab injection within the recommended timeframe. Over time, more than half of the patients did not change the dose of lenvatinib, and most patients had the same dose of pembrolizumab. On average, patients were treated with lenvatinib and pembrolizumab for 5­6 months. This study showed that in general, patients were taking lenvatinib and pembrolizumab for treatment of EC as recommended by product labels.

Real-world prevalence of microsatellite instability testing and related status in women with advanced endometrial cancer in Europe.

PURPOSE: To assess the real-world prevalence of microsatellite instability (MSI)/mismatch repair (MMR) testing and related tumor status in recurrent/advanced endometrial cancer patients in Europe. METHODS: Data were from two multi-center, retrospective patient chart review studies conducted in the United Kingdom, Germany, Italy, France and Spain: The Endometrial Cancer Health Outcomes-Europe-First-Line (ECHO-EU-1L) study and the ECHO-EU-Second-Line (ECHO-EU-2L) study. ECHO-EU-1L included recurrent/advanced endometrial cancer patients who received first-line systemic therapy between 1/JUN/2016 and 31/MAR/2020 after recurrent/advanced diagnosis. ECHO-EU-2L included patients with recurrent/advanced endometrial cancer who progressed between 1/JUN/2016 and 30/JUN/2019 following prior first-line systemic therapy. Data collected included patient demographics, MSI/MMR tumor testing and results, and clinical/treatment characteristics. RESULTS: ECHO-EU-1L included 242 first-line patients and ECHO-EU-2L included 475 s-line patients. For all patients, median age at recurrent/advanced diagnosis was 69 years, roughly half had endometrioid carcinoma histology and over 75% had Stage IIIB-IV disease at initial diagnosis. The prevalence of MSI/MMR testing in the first-line and second-line cohorts was similar (36.4 and 34.9%, respectively). Among those tested, a majority had non-MSI-high/MMR proficient tumors (80.7 and 74.7% among first- and second-line patients, respectively). About 15% had MSI-high/MMR deficient tumors in both cohorts, and a few patients had discordant results (3.4 and 10.8% among first- and second-line patients, respectively). CONCLUSION: Prior to the approvals of biomarker-directed therapies for recurrent/advanced endometrial cancer patients in Europe, there were low MSI/MMR testing rates for these patients of just over one-third. Given the availability of biomarker-directed therapies, increased MSI/MMR testing may help inform treatment decisions for recurrent/advanced endometrial cancer patients in Europe.

Treatment patterns and real-world clinical outcomes in patients with advanced endometrial cancer who are microsatellite instability (MSI)-high or are mismatch repair deficient (dMMR) in the United States.

OBJECTIVES: Microsatellite instability-high (MSI-H) and deficient DNA mismatch repair (dMMR) status have emerged as actionable biomarkers for advanced endometrial cancer (aEC). The objective of this study was to assess clinical outcomes and treatment patterns among MSI-H/dMMR aEC patients who had disease progression following prior systemic therapy (FPST) in the US. METHODS: Endometrial Cancer Health Outcomes (ECHO) was a retrospective, medical chart review study of patients with MSI-H/dMMR aEC who had disease progression between 07/01/2016 and 12/31/2018 FPST and were not candidates for curative surgery. Data on patient demographics, clinical and treatment characteristics, and clinical outcomes were collected. Kaplan-Meier analyses were performed to estimate real-world progression-free survival (rwPFS) and overall survival (OS), stratified by drug class. RESULTS: A total of 124 eligible patients who initiated second-line chemotherapy ± bevacizumab or immunotherapy were included. Mean age was 61.4 years at aEC diagnosis and 86.3% of patients were stage IIIB-IV. Median rwPFS and OS were 4.0 months (95% CI: 2.0-9.0) and 7.0 months (95% CI: 5.0-18.0), respectively, among 21 patients who received chemotherapy ± bevacizumab, and 29.0 months (95% CI: 18.0-NE) and not reached (95% CI: 30.0-NA), respectively, among 103 patients who received immunotherapy. Most patients (n = 92) received pembrolizumab; among these patients, rwPFS and OS were 29.0 months (95% CI: 18.0-NE) and 30 months (95% CI: 30.0-NA), respectively. CONCLUSIONS: Real-world evidence suggests that pembrolizumab monotherapy provides considerable clinical benefits and has become the standard of care for MSI-H/dMMR aEC patients FPST who are not candidates for curative surgery in real-world settings.

Relative importance of individual insurance status and hospital payer mix on survival for women with cervical cancer.

OBJECTIVE: To assess the relative contributions of individual insurance status and hospital payer mix (safety net status) to quality of care and survival for patients with cervical cancer. METHODS: We used the National Cancer Database to identify patients with cervical cancer diagnosed from 2004 to 2017. Patients were classified by insurance (uninsured/Medicaid/private/Medicare/other) and hospitals were grouped into quartiles based on the proportion of uninsured/Medicaid patients (payer mix) (top quartile defined as safety-net hospital (SNHs) and lowest as Q1 hospitals). Quality-of-care was assessed by adherence to evidence-based metrics. Individual contributions of insurance status and payer mix to survival was assessed with a proportional hazards Cox model. RESULTS: A total of 124,339 patients including 11,338 uninsured (9.1%) and 27,281 Medicaid (21.9%) recipients treated at 1156 hospitals were identified. Quality-of-care was not significantly different across hospital quartiles. Adjusting for patients' clinical/demographic characteristics, treatment at a SNH was associated with a 14% higher mortality (HR = 1.14; 95% CL, 1.08-1.20) than at Q1 hospitals. Testing for individual insurance, uninsured patients had 32% increased mortality (HR = 1.32; 95% CI,1.26-1.38) and Medicaid recipients 40% increased (HR = 1.40; 95%CI,1.35-1.44) compared to privately insured patients. Examining both payer mix and insurance, only individual insurance retained a significant impact on mortality. CONCLUSIONS: Individual insurance may be a more important predictor of survival than site-of-care and hospital payer mix for women with cervical cancer. There is substantial variation in outcomes within hospitals based on individual insurance, regardless of hospital payer mix.

Burden of CIN2+ diagnoses and conizations in women aged 18-45 years-a retrospective secondary data analysis of German statutory health insurance claims data.

PURPOSE: High grade cervical intraepithelial neoplasia (CIN2+) may progress to cervical cancer. They may be detected by screening and are usually treated by conization. This study aimed at assessing annual proportions of screening, prevalent and incident CIN2+ diagnoses, as well as proportions of (re-)conizations during 24 months follow-up after conization in Germany. METHODS: A descriptive retrospective claims data analysis of the years 2013-2018 was conducted using the InGef Research Database. Women aged 18-45 years with CIN2+ diagnoses were identified by ICD-10-GM codes (N87.1, N87.2, D06.-, and C53.-). Cervical conizations were identified by OPS codes (5-671.0* or 5-671.1*). Screening participation was identified by EBM codes (01730, 01733, 32819 or 32820). Annual proportions were calculated as women with the respective documented codes divided by all women in the respective age group per calendar year. RESULTS: Overall annual proportions of screened women spanned from 60.01 to 61.33% between 2013 and 2018. The overall annual prevalence of CIN2+ diagnoses (regardless of screening participation) ranged from 0.72 to 0.84% between 2013 and 2018, with highest proportions observed in women aged 27-45 years. Also, CIN2+ incidence was highest in women 27-45 years. Annual proportion of women undergoing conization was 0.24% in 2013 and 0.21% in 2018. During a 24-month follow-up period after conization, 2.91% of women underwent a re-conization 3 months or later after the initial conization. CONCLUSION: This analysis demonstrates a considerable burden of CIN2+, conizations and re-conizations in Germany, especially in women aged 27-45 years. This highlights the need for intensified prevention efforts such as expanding human papillomavirus (HPV) vaccination.

The impact and cost-effectiveness of 9-valent human papillomavirus vaccine in adolescent females in Hong Kong.

INTRODUCTION: In Hong Kong (HK), a single-cohort vaccination program for 10-12-year-old girls with the 9-valent human papillomavirus (HPV) vaccine (9vHPV; types 6/11/16/18/31/33/45/52/58) has been launched. This study assessed the public health impact and cost-effectiveness of implementing routine 9vHPV vaccination (12-year-olds) with or without catch-up 9vHPV vaccination (13-18-year-olds) in HK. METHODS: The health impact and costs of implementing routine 9vHPV vaccination with or without catch-up vaccination over a 100-year time horizon were evaluated using a validated HPV-type transmission dynamic model adapted to the HK population; analyses were performed from a healthcare payer perspective. Routine vaccination (12-year-old girls) and catch-up vaccination (13-18 years) assumed vaccine coverage rates of 70% (base case) and 30%, respectively. The model also assumed herd immunity, lifelong vaccine protection, a discount rate of 3%, and a cost per dose of HK dollars (HKD) 858 [United States dollars (USD) 110] and HKD 1390 (USD 179) for the 2-valent HPV (2vHPV) and 9vHPV vaccines, respectively. HPV disease-related incidence and the incremental cost-effectiveness ratio (ICER) per quality-adjusted-life-year (QALY) were estimated. Cost-effectiveness was determined at a ceiling threshold of HK dollars (HKD) 382,046 (USD 49,142) or 1.0 times the gross domestic product per capita of HK. RESULTS: Compared with routine 9vHPV alone, routine plus catch-up 9vHPV is projected to reduce cervical cancer incidence by 3.4%. Routine plus catch-up 9vHPV will also reduce genital warts incident cases for males/females by 2.6%/5.4%. The incremental cost-effectiveness ratios were HKD 29,911 (USD 3847)/quality-adjusted life-year (QALY) for routine plus catch-up 9vHPV versus routine 9vHPV alone and HKD 25,524 (USD 3283)/QALY for routine 9vHPV alone versus screening only. Sensitivity analyses indicated that routine plus catch-up 9vHPV compared with routine 9vHPV alone remained cost-effective at coverage rates of 30% and 90%. CONCLUSIONS: This analysis predicts that the current HK vaccination strategy can be considered cost-effective and will provide maximum health benefit. These results support addition of the routine 9vHPV vaccine with or without catch-up 9vHPV vaccination to the regional vaccination program in HK.

HPV vaccination uptake and administration from 2006 to 2016 in a commercially insured population of the United States.

BACKGROUND: Human papillomavirus (HPV) infection can cause various cancers and can be prevented through vaccination. The American Cancer Society (ACS) has set an HPV vaccination completion target in 13-year-old children to 80% by 2026. While HPV vaccine coverage (proportion ever vaccinated) estimates are available, annual uptakes (proportion initiating vaccine in a year) in the United States (U.S.) are not well-known. METHODS: We analyzed MarketScan® claims database to assess HPV vaccination uptakes in the U.S. among the 9- to 26-year-olds in 2006-2016. The annual uptake was the ratio of the number of enrollees who had a first record of an HPV vaccine during the year, and the number of enrollees of similar age and sex that year. RESULTS: Uptake was below 1% among children turning 9 and 10 years old during the year. Since 2009 among female and since 2013 among males, the annual uptake has been the highest in those turning 13 years old (19.7% among females and 17.6% among males in 2016). Catch-up vaccination among older adolescents and young adults increased after Advisory Committee for Immunization Practices (ACIP) recommendations, but eventually slowed down as more younger persons were vaccinated. Most young adolescents were vaccinated by pediatricians, whereas young adult women were predominantly vaccinated by obstetricians/gynecologists and young adult males by family physicians. While only about half of the adolescents had well-check visits, the majority of those who initiated HPV vaccination had one the same year. CONCLUSION: Continued increase in uptake is needed to reach the ACS 2026 goals.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States.

Background: The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods: This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results: A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI, $8849-$12446), respectively. Conclusions: The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

Background: Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. Methods: A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. Results: The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Conclusions: Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI.

Thirty-Day Readmissions in Hospitalized Patients Who Received Bezlotoxumab With Antibacterial Drug Treatment for Clostridium difficile Infection.

Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam as empiric therapy based on the in-vitro surveillance of bacterial isolates in the United States for the treatment of complicated urinary tract infections.

BACKGROUND: A challenge in the empiric treatment of complicated urinary tract infection (cUTI) is identifying the initial appropriate antibiotic therapy (IAAT), which is associated with reduced length of stay and mortality compared with initial inappropriate antibiotic therapy (IIAT). We evaluated the cost-effectiveness of ceftolozane/tazobactam compared with piperacillin/tazobactam (one of the standard of care antibiotics), for the treatment of hospitalized patients with cUTI. METHODS: A decision-analytic Monte Carlo simulation model was developed to compare the costs and effectiveness of empiric treatment with either ceftolozane/tazobactam or piperacillin/tazobactam in hospitalized adult patients with cUTI infected with Gram-negative pathogens in the US. The model applies the baseline prevalence of resistance as reported by national in-vitro surveillance data. RESULTS: In a cohort of 1000 patients, treatment with ceftolozane/tazobactam resulted in higher total costs compared with piperacillin/tazobactam ($36,413 /patient vs. $36,028/patient, respectively), greater quality-adjusted life years (QALYs) (9.19/patient vs. 9.13/patient, respectively) and an incremental cost-effectiveness ratio (ICER) of $6128/QALY. Ceftolozane/tazobactam remained cost-effective at a willingness to pay of $100,000 per QALY compared to piperacillin/tazobactam over a range of input parameter values during one-way and probabilistic sensitivity analysis. CONCLUSIONS: Model results show that ceftolozane/tazobactam is likely to be cost-effective compared with piperacillin/tazobactam for the empiric treatment of hospitalized cUTI patients in the United States.

Epidemiological and economic burden of Clostridium difficile in the United States: estimates from a modeling approach.

BACKGROUND: Despite a large increase in Clostridium difficile infection (CDI) severity, morbidity and mortality in the US since the early 2000s, CDI burden estimates have had limited generalizability and comparability due to widely varying clinical settings, populations, or study designs. METHODS: A decision-analytic model incorporating key input parameters important in CDI epidemiology was developed to estimate the annual number of initial and recurrent CDI cases, attributable and all-cause deaths, economic burden in the general population, and specific number of high-risk patients in different healthcare settings and the community in the US. Economic burden was calculated adopting a societal perspective using a bottom-up approach that identified healthcare resources consumed in the management of CDI. RESULTS: Annually, a total of 606,058 (439,237 initial and 166,821 recurrent) episodes of CDI were predicted in 2014: 34.3 % arose from community exposure. Over 44,500 CDI-attributable deaths in 2014 were estimated to occur. High-risk susceptible individuals representing 5 % of the total hospital population accounted for 23 % of hospitalized CDI patients. The economic cost of CDI was $5.4 billion ($4.7 billion (86.7 %) in healthcare settings; $725 million (13.3 %) in the community), mostly due to hospitalization. CONCLUSIONS: A modeling framework provides more comprehensive and detailed national-level estimates of CDI cases, recurrences, deaths and cost in different patient groups than currently available from separate individual studies. As new treatments for CDI are developed, this model can provide reliable estimates to better focus healthcare resources to those specific age-groups, risk-groups, and care settings in the US where they are most needed. (Trial Identifier ClinicaTrials.gov: NCT01241552).

Real-world treatment patterns and clinical outcomes from a retrospective chart review study of patients with recurrent or advanced endometrial cancer who progressed following prior systemic therapy in Europe.

OBJECTIVE: To evaluate real-world treatment patterns and clinical outcomes in recurrent/advanced endometrial cancer patients who progressed following prior systemic therapy in clinical practice in Europe. DESIGN: Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a retrospective patient chart review study. SETTING: ECHO-EU is a multicentre study conducted in the UK, Germany, Italy, France and Spain. PARTICIPANTS: Patients with recurrent/advanced endometrial cancer who progressed between 1 July 2016 and 30 June 2019 following prior first-line systemic therapy were eligible and data were collected until last available follow-up through November 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Data collected included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed since initiation of second-line therapy to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS) and overall survival (OS). RESULTS: A total of 475 patients were included from EU5 countries. Median age was 69 years at advanced endometrial cancer diagnosis, 78.7% had stage IIIB-IV disease, 45.9% had Eastern Cooperative Oncology Group status ≥2 at second-line therapy initiation. In second line, a majority of patients initiated either non-platinum-based chemotherapy (55.6%) or endocrine therapy (16.2%). Physician-reported real-world overall response rate (classified as complete or partial response) to second-line therapy was 34.5%, median rwPFS was 7.4 months (95% CI 6.2 to 8.0) and median OS was 11.0 months (95% CI 9.9 to 12.3). CONCLUSIONS: Patients had poor clinical outcomes with a median OS of <1 year and rwPFS of approximately 7 months, highlighting the significant unmet medical need in pretreated recurrent/advanced endometrial cancer patients. Novel therapies with potential to improve PFS and OS over conventional therapies could provide significant clinical benefit.

Corrigendum to "Adjuvant and first line chemotherapy use for endometrial cancer" [Gynecol. Oncol. Rep. 41 (2022) 101002].

[This corrects the article DOI: 10.1016/j.gore.2022.101002.].

Health-Related Quality of Life in Patients With Advanced Endometrial Cancer Treated With Lenvatinib Plus Pembrolizumab or Treatment of Physician's Choice.

PURPOSE: Lenvatinib and pembrolizumab (LEN+PEMBRO) demonstrated clinically meaningful and statistically significant improvements in efficacy versus treatment of physician's choice (TPC) in patients with advanced endometrial cancer (aEC) in the phase 3 Study 309/KEYNOTE-775. Health-related quality-of-life (HRQoL) is reported. PATIENTS AND METHODS: Patients were randomly assigned to receive LEN+PEMBRO (n = 411; LEN 20 mg/day; PEMBRO 200 mg Q3W) or TPC (n = 416; doxorubicin 60 mg/m2 Q3W or paclitaxel 80 mg/m2 [weekly, 3 weeks on/1 week off]). Impact of treatment on HRQoL assessed by the global health status/quality of life (GHS/QoL) score of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) was a secondary objective; other scales of the Quality-of-Life Questionnaire (QLQ-C30), EORTC QLQ-Endometrial, 24 questions (EORTC QLQ-EN24), and EuroQoL 5 dimensions, 5 levels (EQ-5D-5L) were exploratory objectives. HRQoL was assessed on day 1 of each cycle. Completion/compliance, change from baseline, time to first and definitive deterioration were assessed. No multiplicity adjustments were applied for HRQoL endpoints. RESULTS: The latest timepoint at which the predefined rates of completion (≥60%) and compliance (≥80%) were met was week 12. HRQoL at week 12 between treatment groups was generally similar. Time to first deterioration symptom scales favoured LEN+PEMBRO for QLQ-C30 dyspnoea, and QLQ-EN24 for poor body image, tingling/numbness, and hair loss; and TPC was favoured for QLQ-C30 pain, appetite loss, and diarrhoea, and QLQ-EN24 muscular pain. While the QLQ-C30 physical functional scale favoured TPC, other functional scales were generally similar between arms. Time to definitive deterioration favoured LEN+PEMBRO on most scales. CONCLUSION: HRQoL data from Study 309/KEYNOTE-775, with previously published efficacy and safety results, indicate that LEN+PEMBRO has an overall favourable benefit/risk profile versus TPC for the treatment of patients with aEC. CLINICALTRIALS: GOV: NCT03517449.

Adjuvant and first line chemotherapy use for endometrial cancer.

Objective: The objective of this study was to describe patterns of utilization of cytotoxic, hormonal, and immunotherapy in patients with endometrial cancer in the adjuvant setting and at the time of first recurrence. Methods: We identified patients in the IBM MarketScan database with endometrial cancer who underwent hysterectomy from 2011 to 2019. The use of clinically relevant therapeutic agents and combination regimens was determined in the adjuvant setting and at the time of first recurrence. Results: A total of 22,632 patients were identified. Of these, 7,147 patients (31.6%) received adjuvant radiation and 4,381 (19.4%) received adjuvant chemotherapy following surgery. Of those who received adjuvant chemotherapy, the most commonly utilized agents were carboplatin (90.3%), paclitaxel (85.8%), cisplatin (9.4%), docetaxel (9.3%), gemcitabine (3.8%), and doxorubicin (2.0%), while bevacizumab was utilized in 1.5% of patients. A combination of platinum and a taxane were utilized as adjuvant therapy in 88.8% of women. Of the cohort, 1,825 patients (8.1%) recurred, of whom 1,017 patients had already received adjuvant chemotherapy. The median time from hysterectomy to initiation of chemotherapy for recurrence was 13.3 months (IQR: 7.6-23.1 months). Overall, platinum and taxane combination therapy was used in 788 (46.8%) of patients with recurrent disease, platinum alone or with other drugs in 194 (11.5%), taxanes alone or with other drugs in 145 (8.6%), and non-platinum and non-taxane based therapy in 31.3%. Conclusions: Among patients with endometrial cancer who underwent hysterectomy, platinum-taxane combination chemotherapy was used in almost 90% of patients who received adjuvant chemotherapy while nearly 70% of patients who recurred were treated with platinum or taxane based therapy at first recurrence.

Treatment patterns and real-world clinical outcomes in patients with advanced endometrial cancer that are non-microsatellite instability high (non-MSI-high) or mismatch repair proficient (pMMR) in the United States.

Objective: Microsatellite instability (MSI) due to defective DNA mismatch repair has emerged as an actionable biomarker in advanced endometrial cancer (aEC). Currently, there are no treatment patterns and outcomes data in non-MSI-high (non-MSI-H) or mismatch repair proficient (pMMR) aEC patients following prior systemic therapy (FPST). Our goal was to describe real-world data in this population in the US in 2019 and prior years. Methods: Endometrial Cancer Health Outcomes (ECHO) is a retrospective patient chart review study conducted in the US. Patients with non-MSI-H/pMMR aEC and progression between 06/01/2016-06/30/2019 FPST were eligible. Data collected included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS), and overall survival (OS), separately by treatment category. Results: A total of 165 eligible patients initiated second-line therapy with chemotherapy ± bevacizumab (n = 140) or hormonal therapy (n = 25). Median age was 66.0 years at aEC diagnosis, 70.2% were Stage IIIB-IV, 40.0% had ECOG ≥ 2 at second-line therapy initiation. Median rwPFS was 5.0 months (95% CI: 4.0-6.0) for patients receiving chemotherapy ± bevacizumab and 5.5 months (95% CI: 3.0-29.0) for those receiving hormonal therapy. Median OS was 10.0 months (95% CI: 8.0-13.0) and 9.0 months (95% CI: 6.0-NA) in these groups, respectively. Conclusions: Non-MSI-H/pMMR patients who initiated second-line therapy with chemotherapy ± bevacizumab or hormonal therapy had poor clinical outcomes with a median survival less than 1 year and rwPFS less than 6 months. This was the first study to define the clinical unmet need in patients with non-MSI-H/pMMR aEC with conventional therapy.

Healthcare Costs and Resource Use Associated With Cervical Intraepithelial Neoplasia and Cervical Conization: A Retrospective Study of German Statutory Health Insurance Claims Data.

Background: Cervical intraepithelial neoplasia (CIN) can be a consequence of human papillomavirus (HPV) infection. High-grade CIN (CIN2/CIN3) may develop from persistent HPV infection and progress to cervical cancer if left untreated. Management of CIN includes conservative surveillance or ablation and excision by conization. Internationally, CIN and its treatment generate a considerable economic burden, but no current data regarding costs and resource use from the perspective of the German statutory health insurance exist. Objectives: The aim of this study was to explore the health economic burden in women with CIN diagnoses who either underwent cervical conization or were managed conservatively. Methods: We conducted a retrospective claims data analysis using the InGef Research Database from 2013 to 2018. Healthcare costs and resource utilization in a 24-month observation period (1:1:1 matching) were compared in 18- to 45-year-old women with CIN (1-3) who underwent a conization procedure (study cohort 1) and in women with CIN (1-3) who did not undergo conization (study cohort 2) to women with neither CIN nor conization (control group). Results: For each group, 2749 women were identified. Mean total healthcare costs after 24 months were higher in study cohort 1 (€4446, P<.01) and study cohort 2 (€3754, P=.09) compared with the control group (€3426). Comparing study cohort 1 and 2 to controls, mean differences were highest in age groups 41-45 years (cohort 1: €5115 vs €3354, P<.01; cohort 2: €4152 vs €3354, P=.14). Significantly more women were hospitalized at least once in study cohort 1 (57.46%, P<.01) and study cohort 2 (38.74%, P<.01) compared with the control group (31.14%). Frequency of outpatient physician visits was significantly higher in both study cohorts (43.23 visits, P<.01 and 38.60 visits, P<.01) compared with the control group (32.07 visits). Conclusion: Our results revealed 30% and 10% increased total healthcare costs in women with CIN undergoing invasive treatment (study cohort 1) and conservative management (study cohort 2), respectively, compared with a control group of women with no CIN in a 2-year follow-up period.

Estimating the burden of 2009 pandemic influenza A (H1N1) in the United States (April 2009-April 2010).

To calculate the burden of 2009 pandemic influenza A (pH1N1) in the United States, we extrapolated from the Centers for Disease Control and Prevention's Emerging Infections Program laboratory-confirmed hospitalizations across the entire United States, and then corrected for underreporting. From 12 April 2009 to 10 April 2010, we estimate that approximately 60.8 million cases (range: 43.3-89.3 million), 274,304 hospitalizations (195,086-402,719), and 12,469 deaths (8868-18,306) occurred in the United States due to pH1N1. Eighty-seven percent of deaths occurred in those under 65 years of age with children and working adults having risks of hospitalization and death 4 to 7 times and 8 to 12 times greater, respectively, than estimates of impact due to seasonal influenza covering the years 1976-2001. In our study, adults 65 years of age or older were found to have rates of hospitalization and death that were up to 75% and 81%, respectively, lower than seasonal influenza. These results confirm the necessity of a concerted public health response to pH1N1.