Real-world time on treatment with immuno-oncology therapy in recurrent/metastatic head and neck squamous cell carcinoma.

Aim: We report real-world time on treatment (rwToT) with immuno-oncology (I-O) and other systemic therapies in second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) previously treated with platinum therapies. Materials & methods: Adult patients receiving first-line platinum therapy for R/M HNSCC between January 2017 and December 2018 and a second-line therapy were selected from a US electronic medical record database. Results: In our study sample of 619 R/M HNSCC patients, second-line treatments primarily included I-O therapies (71%) and resulted in median rwToT of 2.8 months and 12-month on-treatment rate of 19.3%. For other second-line therapies, median rwToT and 12-month on-treatment rate was 1.9 months and 1.3%, respectively. Conclusion: Use of second-line I-O therapies was common and resulted in rwToT consistent with R/M HNSCC clinical trials.

Lay abstract Head and neck cancer include tumors that develops in the mouth, throat, nose, salivary glands, oral cancers or other areas of the head and neck. When this cancer returns or spreads to another part of the body, systemic chemotherapies are often used with the goal of prolonging survival. Immunotherapy has emerged as a new approach to treat head and neck cancer by using the body's own immune system to kill cancer cells. The purpose of this study was to better understand the use of immunotherapies in patients with head and neck cancer after the cancer has returned or spread to another part of the body. The study showed that immunotherapies were commonly used and resulted in fewer treatment discontinuations in comparison to other systemic chemotherapies. These results support the use of immunotherapies in this patient population.

Temporal phenotyping by mining healthcare data to derive lines of therapy for cancer.

Lines of therapy (LOT) derived from real-world healthcare data not only depict real-world cancer treatment sequences, but also help define patient phenotypes along the course of disease progression and therapeutic interventions. The sequence of prescribed anticancer therapies can be defined as temporal phenotyping resulting from changes in morphological (tumor staging), biochemical (biomarker testing), physiological (disease progression), and behavioral (physician prescribing and patient adherence) parameters. We introduce a novel methodology that is a two-part approach: 1) create an algorithm to derive patient-level LOT and 2) aggregate LOT information via clustering to derive temporal phenotypes, in conjunction with visualization techniques, within a large insurance claims dataset. We demonstrated the methodology using two examples: metastatic non-small cell lung cancer and metastatic melanoma. First, we generated a longitudinal patient cohort for each cancer type and applied a set of rules to derive patient-level LOT. Then the LOT algorithm outputs for each cancer type were visualized using Sankey plots and K-means clusters based on durations of LOT and of gaps in therapy between LOT. We found differential distribution of temporal phenotypes across clusters. Our approach to identify temporal patient phenotypes can increase the quality and utility of analyses conducted using claims datasets, with the potential for application to multiple oncology disease areas across diverse healthcare data sources. The understanding of LOT as defining patients' temporal phenotypes can contribute to continuous health learning of disease progression and its interaction with different treatment pathways; in addition, this understanding can provide new insights that can be applied by tailoring treatment sequences for the patient phenotypes who will benefit.

Family Consumer Behaviors, Adolescent Prediabetes and Diabetes in the National Health and Nutrition Examination Survey (2007-2010).

BACKGROUND: Prediabetes or diabetes (characterized by hemoglobin A1c [HbA1c] levels ≥ 5.7 gm%) has been associated with numerous long-term complications. Family consumer behaviors are important risk factors that lead to impaired glucose tolerance or diabetes. However, few studies have studied the association between the family consumer environment and prediabetes and diabetes in adolescents. OBJECTIVE: The aim of this study was to examine the association between family consumer behaviors (healthy food availability and supermarket spending) and adolescent prediabetes and diabetes (ClinicalTrials.gov identifier #NCT03136289.) Methods: Data from a nationwide survey conducted by the Centers for Disease Control and Prevention (National Health and Nutrition Examination Survey [NHANES] 2007-2010 data) were used for these analyses. Adolescents aged 12-19 years were selected for this study. Bivariate analyses and logistic regression models assessed the relationship between family consumer behaviors and the prevalence of adolescent prediabetes and diabetes. Multivariable models adjusted for age, gender, ethnicity, physical activity, education, income, and household size. RESULTS: A total of 2520 adolescents were eligible for this study. Adolescents with healthier household food availability had negative odds (odds ratio [OR] = 0.74, 95% confidence interval [CI], 0.55-1.00), as did higher log supermarket spending (OR = 0.69; 95% CI, 0.57-0.85). Interaction models demonstrated that adolescent females had more negative odds of prediabetes/diabetes for both healthier food availability (OR = 0.79, 95% CI, 0.39-1.29) and for greater log supermarket spending (OR = 0.69, 95% CI, 0.57-0.85). CONCLUSION: This study shows that both healthy food availability and an increase in supermarket spending were associated with a decreased adjusted prevalence of prediabetes and diabetes in adolescents, with a greater effect in females. These results suggest the need for policy and dietary interventions targeting the consumer environment.

Associations between sociodemographic and clinicopathological factors and breast cancer subtypes in a population-based study.

PURPOSE: This study examines the factors distinguishing breast cancer (BC) subtypes. METHODS: We examined subtypes in 629 women with invasive BC, diagnosed from 2006 to 2012, and enrolled in an epidemiological study in New Jersey. Using molecular characteristics from pathology reports, BCs were categorized as luminal A, luminal B, non-luminal HER2-expressing, or triple-negative breast cancer (TNBC) subtypes. Multinomial logistic models (luminal A as referent) were used to describe BC subtype associations. RESULTS: Women with luminal B tumors were more likely to be younger at diagnosis [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.0-3.4] and to have higher-grade (OR 2.6, 95% CI 1.5-4.7), larger (OR 1.9, 95% CI 1.0-3.6), and Ki67-positive tumors (OR 2.1, 95% CI 1.1-4.0). Women with non-luminal HER2-expressing BCs were more likely to have higher-grade tumors (OR 14.5, 95% CI 5.3-39.7). Women with TNBCs were more likely to be African-American (OR 1.9, 95% CI 1.0-3.4) and to have higher-grade (OR 9.7, 95% CI 5.1-18.4), larger (OR 2.2, 95% CI 1.0-4.8), and Ki67-positive (OR 2.9, 95% CI 1.6-5.2) tumors. Notably, compared to the luminal A subtype, luminal B, non-luminal HER2-expressing, and triple-negative subtypes were more frequently self-detected; however, these associations were attenuated in multivariable models. CONCLUSIONS: These findings suggest that some BC subtypes were associated with features denoting more aggressive phenotypes, namely higher grade, larger size, and Ki67 positivity, and possibly patient self-detection among some women. These findings highlight a need for enhanced screening, particularly among younger women, racial/ethnic minorities, and lower socioeconomic subgroups.

Effect of travel distance and time to radiotherapy on likelihood of receiving mastectomy.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiation therapy (RT) is the standard of care for women with early-stage breast cancer as an alternative to mastectomy. The purpose of this study was to examine the relationship between receipt of mastectomy and travel distance and time to RT facility in New Jersey (NJ). METHODS: Data were collected from a cohort of 634 NJ women diagnosed with early-stage breast cancer. In patients receiving RT, the precise RT facility was used, whereas in patients not receiving RT, surgeons were contacted to determine the location of RT referral. Travel distance and time to RT facility from the patients' residential address were modeled separately using multiple binomial regression to examine their association with choice of surgery while adjusting for clinical and sociodemographic factors. RESULTS: Overall, 58.5 % patients underwent BCS with median travel distance to the radiation facility of 4.8 miles (vs. 6.6 miles for mastectomy) and median travel time of 12.0 min (vs. 15.0 min for mastectomy). Patients residing > 9.2 miles compared with ≤ 9.2 miles from radiation facility were 44 % more likely to receive mastectomy. Additionally, patients requiring > 19 min compared with ≤ 19 min of travel time were 36 % more likely to receive mastectomy. CONCLUSIONS: These data found that travel distance and time from RT facility act as barriers to undergoing BCS in women with early-stage breast cancer. Despite being in an urban region, a significant number of women in NJ with early-stage breast cancer did not receive BCS.

Role of preoperative magnetic resonance imaging in the surgical management of early-stage breast cancer.

PURPOSE: To examine the role of preoperative magnetic resonance imaging (pMRI) on time to surgery and rates of reoperation and contralateral prophylactic mastectomy (CPM) using a population-based study of New Jersey breast cancer patients. METHODS: The study included 289 African-American and 320 white women who participated in the Breast Cancer Treatment Disparity Study and underwent breast surgery for newly diagnosed early-stage breast cancer between 2005 and 2010. Patients were identified through rapid case ascertainment by the New Jersey State Cancer Registry. Association between pMRI and time to surgery was examined by using linear regression and, with reoperation and CPM, by using binomial regression. RESULTS: Half (49.9 %) of the study population received pMRI, with higher use for whites compared with African-Americans (62.5 vs. 37.5 %). After adjusting for potential confounders, patients with pMRI versus those without experienced significantly longer time to initial surgery [geometric mean = 38.7 days; 95 % confidence interval (CI) 34.8-43.0; vs. 26.5 days; 95 % CI 24.3-29.0], a significantly higher rate of CPM [relative risk (RR) = 1.82; 95 % CI 1.06-3.12], and a nonsignificantly lower rate of reoperation (RR = 0.76; 95 % CI 0.54-1.08). CONCLUSIONS: Preoperative MRI was associated with significantly increased time to surgery and a higher rate of CPM, but it did not affect the rate of reoperation. Physicians and patients should consider these findings when making surgical decisions on the basis of pMRI findings.

Raising the Bar for Real-World Data in Oncology: Approaches to Quality Across Multiple Dimensions.

PURPOSE: Electronic health record (EHR)-based real-world data (RWD) are integral to oncology research, and understanding fitness for use is critical for data users. Complexity of data sources and curation methods necessitate transparency into how quality is approached. We describe the application of data quality dimensions in curating EHR-derived oncology RWD. METHODS: A targeted review was conducted to summarize data quality dimensions in frameworks published by the European Medicines Agency, The National Institute for Healthcare and Excellence, US Food and Drug Administration, Duke-Margolis Center for Health Policy, and Patient-Centered Outcomes Research Institute. We then characterized quality processes applied to curation of Flatiron Health RWD, which originate from EHRs of a nationwide network of academic and community cancer clinics, across the summarized quality dimensions. RESULTS: The primary quality dimensions across frameworks were relevance (including subdimensions of availability, sufficiency, and representativeness) and reliability (including subdimensions of accuracy, completeness, provenance, and timeliness). Flatiron Health RWD quality processes were aligned to each dimension. Relevancy to broad or specific use cases is optimized through data set size and variable breadth and depth. Accuracy is addressed using validation approaches, such as comparison with external or internal reference standards or indirect benchmarking, and verification checks for conformance, consistency, and plausibility, selected on the basis of feasibility and criticality of the variable to the intended use case. Completeness is assessed against expected source documentation; provenance by recording data transformation, management procedures, and auditable metadata; and timeliness by setting refresh frequency to minimize data lags. CONCLUSION: Development of high-quality, scaled, EHR-based RWD requires integration of systematic processes across the data lifecycle. Approaches to quality are optimized through knowledge of data sources, curation processes, and use case needs. By addressing quality dimensions from published frameworks, Flatiron Health RWD enable transparency in determining fitness for real-world evidence generation.

Real-World Data Quality Framework for Oncology Time to Treatment Discontinuation Use Case: Implementation and Evaluation Study.

BACKGROUND: The importance of real-world evidence is widely recognized in observational oncology studies. However, the lack of interoperable data quality standards in the fragmented health information technology landscape represents an important challenge. Therefore, adopting validated systematic methods for evaluating data quality is important for oncology outcomes research leveraging real-world data (RWD). OBJECTIVE: This study aims to implement real-world time to treatment discontinuation (rwTTD) for a systemic anticancer therapy (SACT) as a new use case for the Use Case Specific Relevance and Quality Assessment, a framework linking data quality and relevance in fit-for-purpose RWD assessment. METHODS: To define the rwTTD use case, we mapped the operational definition of rwTTD to RWD elements commonly available from oncology electronic health record-derived data sets. We identified 20 tasks to check the completeness and plausibility of data elements concerning SACT use, line of therapy (LOT), death date, and length of follow-up. Using descriptive statistics, we illustrated how to implement the Use Case Specific Relevance and Quality Assessment on 2 oncology databases (Data sets A and B) to estimate the rwTTD of an SACT drug (target SACT) for patients with advanced head and neck cancer diagnosed on or after January 1, 2015. RESULTS: A total of 1200 (24.96%) of 4808 patients in Data set A and 237 (5.92%) of 4003 patients in Data set B received the target SACT, suggesting better relevance of the former in estimating the rwTTD of the target SACT. The 2 data sets differed with regard to the terminology used for SACT drugs, LOT format, and target SACT LOT distribution over time. Data set B appeared to have less complete SACT records, longer lags in incorporating the latest data, and incomplete mortality data, suggesting a lack of fitness for estimating rwTTD. CONCLUSIONS: The fit-for-purpose data quality assessment demonstrated substantial variability in the quality of the 2 real-world data sets. The data quality specifications applied for rwTTD estimation can be expanded to support a broad spectrum of oncology use cases.

Prevalence and correlates of medication non-adherence among kidney transplant recipients more than 6 months post-transplant: a cross-sectional study.

BACKGROUND: Among kidney transplant recipients, non-adherence with immunosuppressive medications frequently precedes allograft loss. We sought to determine the prevalence and correlates of medication non-adherence among kidney transplant recipients. METHODS: We performed a single-center, cross-sectional study of kidney transplant recipients who were at least 6 months post-transplant. We measured self-reported adherence using the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored from 0 to 12, where higher scores indicate increased adherence) and barriers to adherence using the Immunosuppressive Therapy Barriers Scale (ITBS). We also used validated scales to measure perceived stress, health literacy, anxiety, depression, and interpersonal support. RESULTS: The 252 patients included in the study were 59.9% male, 27.0% Black, and at a median of 2.9 years post-transplant (interquartile range [IQR] 1.4-5.8). On the ITAS, 59.1% scored a perfect 12, 26.6% scored 10-11, and 14.3% scored 0-9. In univariate models, non-adherence (defined as ITAS score ≤9) was significantly associated with increased scores on scales for perceived stress (OR 1.12, 95% CI 1.01-1.25) and depression (OR 1.14, 95% CI 1.02-1.28), and with more self-reported barriers to adherence on the ITBS (OR 1.15, 95% CI 1.08-1.22). After adjusting for sociodemographic factors, stress and depression were not associated with non-adherence. Higher scores on the ITBS (corresponding to more self-described barriers to adherence) were associated with lower scores on the ITAS (P < 0.001). Several individual barriers were associated with non-adherence. CONCLUSIONS: Among prevalent kidney transplant recipients, a minority is non-adherent. Practical barriers to adherence may serve as promising targets for future interventions.

Real-World Therapy with Pembrolizumab: Outcomes and Surrogate Endpoints for Predicting Survival in Advanced Melanoma Patients in Germany.

Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman's rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0-35.4) months, the rwPFS was 3.9 months (95%CI 3.5-4.9), the rwTtNT was 10.7 months (95%CI 9.0-12.9), and the rwToT was 6.2 months (95%CI 5.1-6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints.

Real-world effectiveness of pembrolizumab in advanced melanoma: analysis of a French national clinicobiological database.

Aim: To describe real-world pembrolizumab administration and outcomes for advanced melanoma in France. Materials & methods: Using the MelBase longitudinal database, this multicenter historical-prospective study examined treatment and outcomes of patients with nonuveal, unresectable stage III/IV melanoma initiating pembrolizumab from April 2016 to September 2017, with follow-up to September 2019. Kaplan-Meier time-to-event analyses were conducted. Results: Of 223 patients (median age 67; 51% men), 134 (60%), 36 (16%) and 53 (24%) initiated pembrolizumab in first-, second- and third-line, respectively. Median overall survival (months) was 32.6 (95% CI: 20.3-not reached [NR]), 14.4 (8.6-NR) and 9.3 (6.4-NR), respectively. Best real-world tumor response of complete or partial response was recorded for 49, 39 and 26% of patients, respectively. Conclusion: Study results support benefits of pembrolizumab therapy for advanced melanoma.

Caspofungin use in daily clinical practice for treatment of invasive aspergillosis: results of a prospective observational registry.

BACKGROUND: A prospective observational registry assessed real world experience with caspofungin monotherapy or combination therapy for the initial or salvage treatment of proven or probable invasive aspergillosis (IA). METHODS: Data were collected from April 2006 to September 2007 for patients treated with caspofungin for a single episode of IA. Clinical effectiveness was categorized as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT). RESULTS: Consecutive patients (n = 103) with proven or probable IA (per EORTC/MSG criteria) were identified from 11 countries. Malignancy (76.7%), neutropenia (64.1%), allogeneic hematopoietic stem cell transplantation (HSCT, 22.3%), solid organ transplantation (8.7%), autologous HSCT (4.9%), and HIV/AIDS (2.9%) were the most common underlying conditions. Most patients (84.5%) had pulmonary IA. Aspergillus fumigatus was the most frequently isolated species. The majority of patients received caspofungin monotherapy (82.5%) primarily as salvage therapy (82.4%). The main reason for switching to salvage therapy was clinical failure of the first-line therapy (69%). A favorable response at EOCT was seen in 56.4% (57/101) of patients overall, including 56.5% (48/85) and 56.3% (9/16) of patients receiving caspofungin monotherapy and combination therapy, respectively. Favorable response rates in clinically relevant subgroups were: malignancy, 51.9% (41/79); allogeneic HSCT, 56.5% (13/23); and neutropenia at time of hospitalization, 53.0% (35/66). There was a 72.3% (73/101) survival at 7 days after EOCT. Serious adverse events related to caspofungin were reported in 4 cases (3.9%); 3 patients (2.9%) discontinued treatment due to an adverse event related to caspofungin. CONCLUSIONS: Caspofungin was both effective and well tolerated among high-risk patient groups such as those with neutropenia and active malignancies.

Pembrolizumab for Previously Treated, PD-L1-expressing Advanced NSCLC: Real-world Time on Treatment and Overall Survival.

BACKGROUND: Immune checkpoint inhibitors have been rapidly adopted for therapy of advanced non-small-cell lung cancer (aNSCLC) based on clinical trial findings. Our aim was to examine outcomes in United States oncology practice settings for patients prescribed pembrolizumab monotherapy for previously treated, programmed death ligand-1 (PD-L1)-expressing aNSCLC, thus clinically similar to patients in the KEYNOTE-010 trial. PATIENTS AND METHODS: This retrospective observational study used a nationally representative database to identify adult patients with histologically confirmed aNSCLC and PD-L1 tumor proportion score (TPS) ≥ 1% previously treated with platinum-containing chemotherapy (and appropriate tyrosine kinase inhibitor if nonsquamous aNSCLC with EGFR/ALK genomic tumor aberration). Eligible patients initiated pembrolizumab monotherapy from January 1, 2016, to November 29, 2018; data cutoff was May 31, 2019. The Kaplan-Meier method was used to estimate real-world time on treatment (rwToT) and overall survival (OS). RESULTS: The 349 eligible patients included 199 (57%) men; the median age was 68 years (range, 37-84 years); 70 (25%) of 278 patients with known performance status had Eastern Cooperative Oncology Group score ≥ 2. The median patient follow-up was 8.1 months (range, 1 day to 39.2 months). The median rwToT was 4.9 months (95% confidence interval [CI], 3.7-5.8 months) overall and 5.8 months (95% CI, 4.2-6.6 months) for the TPS ≥ 50% cohort (n = 218). The median OS was 13.8 months (95% CI, 11.0-16.5 months) and 16.5 months (95% CI, 13.7-22.0 months) overall and for TPS ≥ 50%, respectively; 12-month survival rates were 54% and 60%, respectively. CONCLUSION: Patients treated at oncology practices with pembrolizumab monotherapy for previously treated PD-L1-expressing aNSCLC experienced rwToT and OS similar to treatment duration and OS in phase III clinical trial settings.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Outcomes of first-line pembrolizumab monotherapy for PD-L1-positive (TPS ≥50%) metastatic NSCLC at US oncology practices.

Aim: To determine real-world outcomes with first-line pembrolizumab monotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor expression ≥50%. Methods: This retrospective study included adults with ECOG 0-1 initiating first-line pembrolizumab monotherapy on/after 24 October 2016 (EHR cohort) or from 1 December 2016 through 30 November 2017 (spotlight cohort) with ≥6-month follow-up. We estimated Kaplan-Meier overall survival (OS, both cohorts), and, for spotlight, real-world progression-free survival (rwPFS) by Kaplan-Meier and real-world tumor response (rwTR). Results: For 423 patients in the EHR cohort and 188 in spotlight, median OS was 18.9 months (95% CI: 14.9-25.5) and 19.1 months (12.6-not reached), respectively. For spotlight, median rwPFS was 6.8 months (5.3-8.1); rwTR of complete/partial response was 48% (41-56%). Conclusion: Observed OS, rwPFS and rwTR were consistent with clinical trial findings.

First-line pembrolizumab monotherapy for metastatic PD-L1-positive NSCLC: real-world analysis of time on treatment.

Aim: To determine real-world time on treatment (rwToT) with first-line pembrolizumab monotherapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥50%. Methods: The Kaplan-Meier rwToT was estimated from electronic health record data for adults who initiated first-line pembrolizumab monotherapy for stage IV, PD-L1 TPS ≥50% NSCLC, with negative/unknown EGFR/ALK aberrations, and ≥6 months' follow-up until database cutoff. Results: A total of 386 patients with ECOG 0-1 had a median rwToT of 6.9 months (95% CI: 5.6-8.3) and 12-month on-treatment rate of 36.4% (31.2-41.6) versus 40.3% (32.5-47.9) and 37.6% (31.9-43.4) in KEYNOTE-024 (KN024) and KN042 (stage IV/TPS ≥50% subpopulation), respectively. The 24-month restricted-mean rwTOT (extrapolated) was 10.5 months (9.4-11.7), versus 11.0 (9.5-12.5) and 10.4 (9.3-11.5) in KN024 and KN042, respectively. Conclusion: First-line pembrolizumab monotherapy rwToT in metastatic PD-L1 TPS ≥50% NSCLC for trial-matched patients is similar to treatment duration in KN024 and KN042.

Q-TWiST Analysis to Assess Benefit-Risk of Pembrolizumab in Patients with PD-L1-Positive Advanced or Metastatic Non-small Cell Lung Cancer.

OBJECTIVES: Pembrolizumab monotherapy showed significantly longer overall survival and fewer treatment-related adverse events compared to chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1)-positive tumors in the first-line setting in KEYNOTE (KN)-024 and in those previously treated in KN010. The objective of this analysis was to assess the benefit-risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials. METHODS: The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments. Survival time was partitioned into three health states: with toxicity before disease progression, without toxicity before disease progression, and disease progression until death. Health state utilities were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in the trials. Q-TWiST was calculated as the utility-weighted sum of the mean health state durations. Trial data analyzed included the primary analysis and subsequent data cutoffs. The base-case analysis was based on the most recent analysis of the trials. RESULTS: Patients randomized to pembrolizumab had 2.49 months greater Q-TWiST (P value < 0.001) compared to those randomized to platinum-based chemotherapy at a follow-up of 24 months in KN024, and 2.29 months greater Q-TWiST (P value < 0.001) compared to docetaxel over 30 months follow-up in KN010. Results across the trial analyses showed an increase in trend for the Q-TWiST improvement of pembrolizumab over time. CONCLUSIONS: Pembrolizumab showed significant improvement in Q-TWiST compared to chemotherapy in advanced or metastatic NSCLC in both previously untreated and treated patients. The benefits of pembrolizumab continued to accrue with longer follow-ups.

Adverse Outcomes Among Asian Indian Singleton Births in New Jersey, 2008-2011.

The study determined the incidence of low birth weight (LBW), small for gestational age (SGA), preterm birth, and perinatal morbidity among Asian Indians (AI) in New Jersey (NJ), as well as identified predictors of SGA. We analyzed birth records for singletons born to mothers identified as AI and non-Hispanic white from 2008 to 2011, obtained from the NJ Department of Health. For AI, rates of LBW and SGA were elevated, rates of preterm birth were similar, and neonatal intensive care unit admission was lower, compared to whites. Factors associated with SGA in AI included nulliparity, anemia, hypertension, placental abruption, and lack of prenatal care. Maternal education, marital status, substance abuse, and timing of prenatal care were associated with SGA in whites, but not in AI. SGA incidence was higher among AI despite preterm rates similar to whites. Anemia was associated with SGA uniquely among AI.

Diagnosis and surgical delays in African American and white women with early-stage breast cancer.

BACKGROUND: Delays in diagnosis and treatment for breast cancer may contribute to excess deaths among African Americans. We examined racial differences in delays in diagnosis and surgical treatment for early-stage breast cancer and evaluated race-specific predictors associated with delay. METHODS: A retrospective cohort study was conducted among 634 African American and white women diagnosed with invasive breast cancer between 2005 and 2010 in New Jersey. Detailed medical-chart abstraction and patient interviews were undertaken. Time intervals were calculated from symptom recognition to diagnosis (diagnosis delay) and from diagnosis to first operation (surgical delay). Binomial regression models were used to examine racial differences in delay and factors associated with ≥2 months delay in the overall population and stratified by race. Reasons responsible for diagnosis delay were also examined by race. RESULTS: Compared to white women, African American women experienced significantly higher risk of ≥2 months delay in diagnosis and surgical treatment (adjusted relative risks=1.44 (1.12-1.86) and 3.08 (1.88-5.04), respectively). For the African Americans, predictors of diagnosis delay included mode of detection, insurance, and tumor size; for whites, mode of detection and tumor grade. Surgical delay was associated with operation type and education among African Americans but with operation type and tumor size for whites. Patient-related factors were commonly noted as reasons for diagnosis delay. CONCLUSIONS: These findings emphasize the need to raise further awareness, especially among African American patients and their providers, of the importance of prompt evaluation and treatment of breast abnormalities. Research on effective ways to accomplish this is needed.

Utilization and dosage pattern of echinocandins for treatment of fungal infections in US hospital practice.

OBJECTIVE: With the availability of multiple echinocandins in the US, recommended dosages and dosing schedules vary by agent but actual utilization practices are unknown. The purpose of this study was to describe the utilization and dosage pattern of intravenous echinocandins for treatment of fungal infections in US hospitals. METHODS: The Premier Perspective Database was used to describe echinocandin use in 332 US hospitals. Adult patients hospitalized from January, 2006 through June, 2007 with at least one billing record for anidulafungin (Eraxis ** ), caspofungin (Cancidas dagger ), or micafungin (Mycamine double dagger ) were included. Hospitalizations with > 1 echinocandin or >or= 1 dosage with an FDA approved indication for fungal prophylaxis were excluded. Mixed multivariable models were developed to identify factors associated with mean daily dose. ** Eraxis, a registered trade name owned by Pfizer, Inc., New York, NY, USA dagger Cancidas, a registered trade name owned by Merck & Co., Inc., Whitehouse Station, NJ, USA double dagger Mycamine, a registered trade name owned by Astellas Pharma US, Inc., Deerfield, IL, USA. RESULTS: The number of unique patient hospitalizations was 708 for anidulafungin, 15 739 for caspofungin, and 1199 for micafungin. A single echinocandin was utilized at 88.6% of hospitals. Micafungin patients had the highest prevalence of cancer, bone marrow transplant, solid organ transplant, HIV/AIDS, fungal infection, and neutropenia. Mean day 1 dose of echinocandin therapy was 171.2 +/- 85.4 mg, 79.7 +/- 25.6 mg, and 154.3 +/- 67.3 mg; and mean day 2 onwards dose was 98.7 +/- 39.4 mg, 53.1 +/- 12.5 mg, 122.6 +/- 39.4 mg for anidulafungin, caspofungin and micafungin, respectively. Commonly used loading doses were 200 mg (55.6%) for anidulafungin, 70 mg (57.2%) for caspofungin, and 200 mg (21.2%) for micafungin. The first-day dose of echinocandin therapy (vs. subsequent days) was most strongly associated with mean daily dose. CONCLUSIONS: In hospital practice, the mean dosages were consistent with the recommended loading and maintenance dosages for caspofungin and anidulafungin. Patients frequently received a loading dose of > 150 mg on day 1 of micafungin which was inconsistent with recommended dosing schedules. Micafungin maintenance dosages > 100 mg were also commonly used. Lack of information on reason for initiating echinocandin therapy was an important study limitation.