Background: Adults with immuno-compromising conditions, CSF leaks, or cochlear implants are at increased risk for pneumococcal disease (high-risk patients), yet pneumococcal vaccination rates in the US for this group are low. Methods: A retrospective cohort analysis was conducted from 2010 to 2018 using the Truven Health MarketScan database to estimate pneumococcal vaccination coverage among adults aged 19 to 64 years newly diagnosed with high-risk conditions, and to assess factors associated with receiving the recommended pneumococcal vaccines. Results: The study sample included 2,497,799 adults aged 19 to 64 years old with newly diagnosed high-risk conditions. Most of the study cohort had seven or more annual physician office (52%) and pharmacy (56%) visits. The proportion of high-risk adults who received at least one pneumococcal vaccination increased from 5.4% after 1 year of follow-up to 14.2% after 6 years of follow-up. Compared to those who received no pneumococcal vaccination, high-risk adults who received any pneumococcal vaccination were more likely to be older, female, enrolled in an HMO, had more healthcare encounters, and were treated by a primary care provider. Conclusion: Despite numerous healthcare encounters annually, very few high-risk adults received pneumococcal vaccines, highlighting the need for implementing targeted interventions to increase vaccine uptake in this vulnerable population.

Background Extraction of line-of-therapy (LOT) information from electronic health record and claims data is essential for determining longitudinal changes in systemic anticancer therapy in real-world clinical settings. Objective The aim of this retrospective cohort analysis is to validate and refine our previously described open-source LOT algorithm by comparing the output of the algorithm with results obtained through blinded manual chart review. Methods We used structured electronic health record data and clinical documents to identify 500 adult patients treated for metastatic non–small cell lung cancer with systemic anticancer therapy from 2011 to mid-2018; we assigned patients to training (n=350) and test (n=150) cohorts, randomly divided proportional to the overall ratio of simple:complex cases (n=254:246). Simple cases were patients who received one LOT and no maintenance therapy; complex cases were patients who received more than one LOT and/or maintenance therapy. Algorithmic changes were performed using the training cohort data, after which the refined algorithm was evaluated against the test cohort. Results For simple cases, 16 instances of discordance between the LOT algorithm and chart review prerefinement were reduced to 8 instances postrefinement; in the test cohort, there was no discordance between algorithm and chart review. For complex cases, algorithm refinement reduced the discordance from 68 to 62 instances, with 37 instances in the test cohort. The percentage agreement between LOT algorithm output and chart review for patients who received one LOT was 89% prerefinement, 93% postrefinement, and 93% for the test cohort, whereas the likelihood of precise matching between algorithm output and chart review decreased with an increasing number of unique regimens. Several areas of discordance that arose from differing definitions of LOTs and maintenance therapy could not be objectively resolved because of a lack of precise definitions in the medical literature. Conclusions Our findings identify common sources of discordance between the LOT algorithm and clinician documentation, providing the possibility of targeted algorithm refinement.

BACKGROUND:The World Health Organization (WHO)-defined radiological pneumonia is a preferred endpoint in pneumococcal vaccine efficacy and effectiveness studies in children. Automating the WHO methodology may support more widespread application of this endpoint.METHODS:We trained a deep learning model to classify pneumonia CXRs in children using the World Health Organization (WHO)'s standardized methodology. The model was pretrained on CheXpert, a dataset containing 224,316 adult CXRs, and fine-tuned on PERCH, a pediatric dataset containing 4,172 CXRs. The model was then tested on two pediatric CXR datasets released by WHO. We also compared the model's performance to that of radiologists and pediatricians.RESULTS:The average area under the receiver operating characteristic curve (AUC) for primary endpoint pneumonia (PEP) across 10-fold validation of PERCH images was 0.928; average AUC after testing on WHO images was 0.977. The model's classification performance was better on test images with high inter-observer agreement; however, the model still outperformed human assessments in AUC and precision-recall spaces on low agreement images.CONCLUSION:A deep learning model can classify pneumonia CXR images in children at a performance comparable to human readers. Our method lays a strong foundation for the potential inclusion of computer-aided readings of pediatric CXRs in vaccine trials and epidemiology studies.

Background. Universal childhood vaccination against varicella began in the United States as a 1-dose schedule in 1996, changing to a 2-dose schedule in 2006. The exogenous boosting hypothesis, which postulates that reexposure to circulating wild-type varicella delays the onset of herpes zoster, predicts a transient increase in the incidence of herpes zoster, peaking in adults 15-35 years after the start of varicella vaccination. Methods. This was a retrospective study of administrative claims data from the MarketScan Commercial and Medicare databases between 1991-2016. Outcome measures were the incidences of herpes zoster per 100 000 person-years, by calendar year and age category, and the annual rates of change in herpes zoster by age category, in an interrupted time series regression analysis, for the periods of 1991-1995 (prevaccine), 1996-2006 (1-dose vaccination period), and 2007-2016 (2-dose vaccination period). Results. The annual incidences of herpes zoster increased throughout the period of 1991-2012 in all adult age categories, with a plateau in 2013-2016 that was most evident in the >= 65 age group. In 1991-1995, the herpes zoster incidences increased at annual rates of 4-6% in age categories 18-34, 35-44, 45-54, and 55-64 years. In the same age categories during 1996-2006 and 2007-2016, the herpes zoster incidences increased at annual rates of 1-5%. Conclusions. Although the annual incidence of herpes zoster in adults has continued to increase, the rates of change decreased during both the 1- and 2-dose vaccination periods. The hypothesized increase in herpes zoster predicted from modelling of the exogenous boosting hypothesis was not observed.

Aim: To determine outcomes of retreatment with anti-PD-1 monotherapy for melanoma. Materials & methods: This retrospective study included adults with unresectable cutaneous melanoma who achieved stable disease (SD) or better after anti-PD-1 monotherapy and were retreated with anti-PD-1 monotherapy after ≥90-day gap. We determined overall survival and real-world tumor response. Results: For 21 eligible patients, from retreatment initiation, median follow-up was 14.4 months (range, 2.6-34.5); median overall survival was 30.0 months (95% CI: 14.4-not reached); 1-year survival was 100% (95% CI: 100-100%); 2-year survival was 83% (48-96%). Of 16 patients with recorded best real-world tumor response, ten (63%) responded (complete/partial response); three achieved SD; three had progressive disease. Conclusion: Patients with advanced melanoma achieving SD/better after first-course anti-PD-1 monotherapy may benefit from retreatment.

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.

Abstract Background The presence of chronic and immunocompromising conditions is associated with a disproportionately high risk of developing pneumococcal disease at older ages. The objective of this study was to quantify the risk of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) in older US adults aged 65 years and older with underlying medical conditions. Methods A retrospective observational study was conducted using the Humana claims database. The study cohorts were identified at January 1 of each calendar year of observation from 2012 to 2017 and comprised adults aged 65 years and older with continuous enrollment for at least one year before and at least one year after January 1 of each year. For each yearly cohort, medical conditions were identified during the one year before each calendar year and episodes of ACP and IPD were identified during the corresponding 1-year follow-up period from January 1 to December 31. Individuals were stratified into 3 groups: those without any medical conditions of interests (healthy), those with chronic conditions (at-risk) and those with immunocompromising conditions (high-risk). Rate of ACP or IPD was expressed as the number of cases per 100,000 person-years and the rate ratio (RR) was expressed as the rate of pneumococcal disease of patients with medical conditions divided by the rate of pneumococcal disease in healthy adults. Results Of the 10,766,827 adults included in the study, 75% of adults had an underlying medical condition linked to an increased risk of pneumococcal disease. In adults with at-risk conditions, rates of ACP and IPD were 3.1 and 3.6 times the rate in healthy adults, respectively. In adults with high-risk conditions, rates of ACP and IPD were 4.1 and 5 times the rate in healthy adults, respectively. Rate of pneumococcal disease increased substantially with the addition of medical conditions: RR for ACP and IPD increased from 2.1 and 2.2, respectively, in adults with one at-risk conditions to 4.8 and 6.2, respectively, among adults with 2 or more at-risk conditions. Conclusion Despite recommendations of universal pneumococcal vaccination in older adults aged 65 years and above in the United States, the burden of pneumococcal disease remains high, particularly among those with chronic and immunocompromising conditions. Disclosures All authors: No reported disclosures.

e21031 Background: Pembrolizumab (PEM), a humanized antibody targeting programmed death-1 receptor, has been approved by FDA for the treatment of patients (pts) with advanced melanoma (AM) in the US since 2014. Real-world (RW) data supports the clinical effectiveness of 1L use of PEM, but there is limited information of PEM later line use. The study examined the RW outcomes of pts treated with PEM who have failed prior lines of therapy in US oncology clinical practices. Methods: Flatiron Health longitudinal database was used to identify adult pts with AM who received ≥1 dose of PEM in second line (2L) or later (3L+) between September 4, 2014 and May 31, 2017. Pts were followed up to May 31, 2018. Pts in clinical trials were excluded. Pt demographic, treatment, and clinical characteristics were described. Time on treatment (ToT) and overall survival (OS) were analyzed using the Kaplan Meier (KM) method, with the first dose of PEM as the starting point. Results: Two hundred thirty-six pts were included in the analysis, of which there were 171 2L and 65 3L+. Overall, median age at PEM initiation was 66 years; most were male (66.1%) and Caucasian (95.4%). 41.1% of pts’ tumors were confirmed BRAF mutant; 49.6% of pts’ tumors were confirmed BRAF wildtype; the rest was not tested or indeterminate. When data were available, 26.2% had an elevated lactate dehydrogenase (> ULN), 24.6% had brain metastases, and 25.5% had an ECOG performance status of > 1. At the time of analysis, pts were followed for a median of 12.5 months (mo, range, 0.1-44.6). Overall median ToT was 4.4 mo (95% CI, 3.5-5.3), with 4.7 and 4.4 mo in 2L and 3L+, respectively. Overall median OS was 16.8 mo (95% CI, 12.2-25.9), with 16.8 and 18.9 mo for 2L and 3L+ respectively. 1-year and 2-year survival, using the KM method, was 58.0% (95% CI, 51.2-64.1; 2L, 57.4%; 3L+, 59.6%) and 44.7% (95% CI, 37.9-51.3; 2L, 44.3%; 3L+, 46.1%) respectively. Conclusions: The study reports RW use of PEM in a large cohort of pts with AM who have failed initial therapy in US oncology clinical practices, with a heterogeneous study population compared to clinical trials. The findings of OS based on RW use suggest PEM is an effective treatment option for patients in later lines of therapy.

Objective: This study investigated the patterns of pneumococcal disease vaccination, the time between two different pneumococcal vaccine doses and factors associated with series completion. Methods: A retrospective claims database analysis was conducted using the Clinformatics DataMart (TM) database. Adults who turned 65 years between January 1st, 2013 to June 30th, 2017 and were continuously enrolled (>= 15 months) in the Medicare Advantage plans to June 30th, 2017 were included in this study. Pneumococcal vaccination patterns included: PCV13-PPV23, PPV23-PCV13, or receiving PPV23 or PCV13 only. Pneumococcal vaccination series completion was defined as receiving PCV13-PPV23 or PPV23-PCV13 from 65 years old to June 30th, 2017 while non-completion was defined as receiving only PCV13 or only PPV23 from 65 years old to June 30th, 2017. A multivariable logistic regression model was used to identify factors associated with pneumococcal vaccination series completion. Results: A total of 224,132 adults were included in this study. Most received no pneumococcal vaccination (49%), while 34.3% received only one vaccine. Series completion occurred in 16.8% of adults. Some adults received only one vaccination: 11.6% received PPV23 and 22.7% received PCV13. The mean time between vaccinations was 420.8 days (approximately 14 months) for the PCV-PPV23 series, and 595.5 days (approximately 20 months) for the PPV23-PCV13 series. Adults were significantly more likely to complete pneumococcal vaccination series if they had at least one doctor's office, outpatient visit, or pharmacy visit versus no visits, or received an influenza vaccination in the first year after turning 65 years than those who did not (All: P < 0.001). Conclusion: Despite the 2014 recommendation, percentages of pneumococcal vaccination series completion were found to be low, aligning with recent literature. This highlights the need to improve series completion, given the increased risk and associated economic burden of pneumococcal disease in adults aged >= 65 years. (C) 2018 Merck Sharp & Dohme Corp. Published by Elsevier Limited.

The mechanism for reactivation of varicella zoster virus as herpes zoster (HZ) is not well understood. One hypothesis postulates that re-exposure to circulating wild-type varicella can boost individual immunity and prevent reactivation (“Exogenous Boosting,” EB). The validity of this hypothesis has been debated and the evidence to evaluate it is limited. Dynamic transmission model outcomes of impact and cost-effectiveness of universal varicella vaccination (UVV) are sensitive to EB characterization and assumptions, occasionally leading to conclusions that UVV programs may not be cost-effective and could lead to temporary increases in HZ incidence. The goal of this study was to use data from 20 years of UVV in the United States from 1996 to 2016 to evaluate whether the hypothesized increases in HZ incidence have been realized. This is a retrospective study of de-identified administrative claims data from the US MarketScan® databases between 1991 and 2016. The incidence of HZ was analyzed by calendar year and age category using interrupted time series (ITS) analysis implemented through a negative binomial generalized linear regression model over three time periods: pre-UVV (1991–1995); 1 dose UVV (1996–2006); and 2 dose UVV (2007–2016). The ITS approach (Bernal et al., IJE, 2017) is an effective way to evaluate the impact of public health interventions implemented at specific time points. HZ incidence in the pre-UVV period increased at annual rates between 3.67% and 12.38%, with the highest increases in the 0–17 and 65+ age groups. The rate of HZ increase was lower in the 1 dose UVV period compared with the pre-UVV period for all age groups except for minor increases in the 18–35 (0.52%) and 55–65 (0.14%) groups. During the 2 dose UVV period, the rate of increase in HZ was lower in all groups than in the pre-UVV period, with the largest reductions in the 0–17 (−22.58%), 65+(−10.68%), and 18–<35 (−3.57%) age groups. This evaluation of the impact of UVV on rates of change in HZ does not support the hypothesis of an increase in HZ incidence due to UVV. While overall HZ incidence rates have been increasing year on year, the rate of that increase has been declining in both UVV periods. Our findings have implications on the assumptions used in economic evaluations of UVV programs. L. Wolfson, Merck & Co., Inc.: Employee and Shareholder, Salary. V. Daniels, Merck & Co., Inc.: Employee and Shareholder, Salary. Y. T. Chen, Merck & Co., Inc.: Employee and Shareholder, Salary. W. Ou, Merck & Co., Inc.: Employee and Shareholder, Salary.

Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan-Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18-84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids <3 months before initiating pembrolizumab. Median study follow-up was 12.9 months (range, 0.03-39.6). Median OS was 21.8 months (95% confidence interval [CI] 16.8-29.1); KM 1-year and 2-year survival rates were 61% and 48%, respectively; and median time on pembrolizumab treatment was 4.9 months (95% CI 3.7-5.5). Median OS for first-line pembrolizumab was not reached, and for second-line and third-line/later was 13.9 and 12.5 months, respectively (log-rank P = .0095). Significantly better OS (all P ≤.0014, log-rank test) was evident for patients with ECOG performance status (PS) of 0 to 1 (vs >1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription <3 months before. No difference was recorded in OS by brain metastases (log-rank P = .22) or BRAF mutation status (log-rank P = .90).These findings support effectiveness of pembrolizumab in the real-world clinical setting and provide important insights into patient characteristics and outcomes associated with pembrolizumab therapy for a heterogeneous patient population with advanced melanoma, including patients who would not be eligible for clinical trials.