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Background The BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−), PIK3CA‐mutated advanced breast cancer (ABC), after cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real‐world setting. Materials and Methods Patients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real‐world patient cohort who received standard‐of‐care from a deidentified clinico‐genomics database (CGDB). Primary and secondary endpoints were to compare progression‐free survival (PFS), estimated by the Kaplan‐Meier method, and the proportion of patients remaining progression‐free at 6 months, respectively, between the two cohorts. Results A total of 855 patients with PIK3CA‐mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2‐targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real‐world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real‐world cohort, and 6‐month PFS was 54.6% versus 40.1%, respectively. Conclusion Matched/weighted analysis comparing BYLieve with the real‐world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2−, PIK3CA‐mutant ABC after CDK4/6i treatment. Implications for Practice Approximately 40% of patients with hormone receptor–positive (HR+), human epidermal growth factor receptor‐2–negative (HER2−) advanced breast cancer (ABC) have PIK3CA‐mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α‐selective phosphatidylinositol‐3‐kinase inhibitor, demonstrated significantly improved progression‐free survival in SOLAR‐1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real‐world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2−, PIK3CA‐mutant ABC in the post‐CDK4/6i setting., This article reports the efficacy of treatment with alpelisib combined with fulvestrant in a cohort of patients with PIK3CA‐mutated breast cancer compared with the effectiveness of real‐world standard treatments in the post‐CDK4/6i setting using data from a deidentified clinico‐genomics database (CGDB).

Summary Background Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A. Methods This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov , NCT03056755 . Findings Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported. Interpretation BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor. Funding Novartis Pharmaceuticals.

Background: The PIK3CA gene encodes phosphatidylinositol-3-kinase (PI3K-α), which plays a central role in the growth, division, and many cellular processes critical for tumorigenesis. PIK3CA alteration is present in up to 40% of patients with HR+/HER2- mBC. Recent advances in therapies targeting the PI3K signaling pathway in breast cancer demonstrate improved outcomes; however, additional understanding on the implication of PIK3CA mutations in treatment sequencing decisions for patients with HR+/HER2- mBC is required. Methods: A retrospective analysis of the Flatiron Health/Foundation Medicine Clinico-Genomics Database, a nationwide database comprising de-identified patient-level structured and unstructured clinical data curated via technology-enabled abstraction and linked to genomic information, was conducted to characterize treatment sequencing among HR+/HER2- mBC patients, stratified by PIK3CA alteration status (PIK3CA+, PIK3CA-), as well as timing of NGS testing. The cohort included patients with follow-up through December 31, 2018, with no patients having received a PI3K inhibitor for mBC during this time. Patients in the cohort had ≥2 clinic visits since Jan 1 2011, chart confirmed diagnosis of HR+/HER2- mBC, and ≥1 Foundation Medicine next-generation sequencing (NGS) test conducted no earlier than 30 days before the mBC diagnosis date (index date). Treatment sequencing analysis included a sub-analysis by de-novo or relapsed mBC and based on sites of metastases and menopausal status. Results are presented as PIK3CA+ vs PIK3CA-, respectively (where applicable). Results: A total of 3,804 BC patients were in the database at the time of the analysis. After applying inclusion criteria, 1,293 patients were included for analysis (521 (40.3%) PIK3CA+, 772 (59.7%) PIK3CA-), median age 59yrs (Q1-Q3: 49-66), 98.8% female. PIK3CA+ patients were slightly older (median 60 vs. 56yrs). The majority of patients received their NGS test during or after 2L of mBC therapy (58% vs 54.9%), while only 5.6% of PIK3CA+ and 9.3% of PIK3CA- patients received NGS before commencing 1L therapy. The most common 1L mBC regimens were chemotherapy (CT) (36%), endocrine therapy (ET) (35%) and CDK4/6-based regimen (CDK4/6) (18%). PIK3CA status by NGS did not have a significant influence on treatment sequencing, however PIK3CA- patients had numerically higher CT than ET as 1L regimen. Common treatments were similar in 2L mBC, with less use of ET and increased use of CDK4/6 across groups. When assessing by menopausal status, the top three 1L treatments were unchanged, however there was a slight increased use of ET (43% vs 35%) and CDK4/6 (21% vs 20%) in post-menopausal patients. The most common sequence of treatments from 1L to 2L (post mBC diagnosis) was two lines of ET for the PIK3CA+ patients (14%) and two lines of CT for the PIK3CA- patients (19%). Two lines of CT was also the most common sequence for 2L to 3L for both groups (12% vs 18%). Remaining treatment sequences demonstrated significant heterogeneity and similar patterns in subgroups assessed. Conclusions: This analysis demonstrated significant heterogeneity of treatment patterns and sequences for both the PIK3CA+ and PIK3CA- groups, which may be expected given the limited available targeted therapies for patients with PIK3CA mutations during the study period. Mutation status is known late in the course of metastatic disease and does not appear to be associated with choice of treatment at this time. Citation Format: Stuart J Turner, Iris Wang, Jinhee Park, Hemanth Kanakamedala, Ines Lorenzo. Treatment sequencing of HR+/HER2- metastatic breast cancer (mBC) patients based on PIK3CA alteration status - A retrospective analysis of a US clinicogenomics database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-20.

A descriptive retrospective study was conducted using the Flatiron Health-Foundation Medicine Inc. (FMI) clinico-genomic database. Patients withOf 91The median time from biopsy to test results appears 1 week shorter for PD-L1 than for FMI NGS. Chemotherapy and IO monotherapy were the most common regimens utilized but with limited PFS.

Background Urinary tract infections (UTIs) are the most common infections caused by Gram-negative bacteria and represent a major healthcare burden. Carbapenem-resistant (CR) strains of Enterobacterales and non-lactose fermenting pathogens further complicate treatment approaches. Methods We conducted a retrospective analysis of the US Premier Healthcare Database (2014–2019) in hospitalised adults with a UTI to estimate the healthcare burden of Gram-negative CR UTIs among patients with or without concurrent bacteraemia. Results Among the 47,496 patients with UTI analysed, CR infections were present in 2076 (4.4%). Bacteraemia was present in 24.5% of all UTI patients, and 1.7% of these were caused by a CR pathogen. The most frequent CR pathogens were Pseudomonas aeruginosa (49.4%) and Klebsiella pneumoniae (14.2%). Patients with CR infections had a significantly longer hospital length of stay (LOS) (median [range] 8 [5–12] days vs 6 [4–10] days, P P P P P Conclusions Among hospitalised patients with UTIs, the presence of a CR organism and bacteraemia increased the burden of disease, with worse outcomes and higher hospitalisation charges than disease associated with CS pathogens and those without bacteraemia.

Sickle cell disease affects more than 30 million people worldwide, including 0.1% of the population in Lebanon. It is characterized by unpredictable and painful vaso-occlusive crises (VOCs) that may lead to serious complications. This study describes the clinical burden of sickle cell disease in a cohort of patients treated at a comprehensive sickle cell disease referral center in Tripoli, Northern Lebanon. Patient demographics, clinical events, treatment, and survival were evaluated from a local, hospital-based registry of 334 sickle cell disease patients treated at the Nini Hospital, Tripoli, Lebanon, between 2009 and 2019. Mean age at sickle cell disease diagnosis and at first clinic visit was 2.9 and 8.5 years, respectively. Pain was the most common clinical event observed among all patients. Over the 10-year follow-up period, 15 (4.5%) patients died. Hydroxyurea (HU) and red blood cell (RBC) transfusions were the most commonly used therapies. One hundred and thirty-one (39.0%) patients were diagnosed with sickle cell disease at the Nini Hospital; the remaining patients were referred to and subsequently followed-up at the Nini Hospital. Eighty-seven (66.0%) Nini Hospital-diagnosed patients experienced a VOC. Seventy-four (85.0%) of these patients with a VOC event required HU during follow-up. Patients with a VOC required more RBC transfusions, cholecystectomy, and splenectomy than non-VOC patients. The high disease burden observed in this population of sickle cell disease patients illustrates a continued, unmet need to both prevent and manage VOC events and other sickle cell disease-associated complications.

Background Serious bloodstream infections (BSIs) are often caused by Gram-negative (GN) bacteria in hospitalized patients. Treatment of these infections has been further complicated by the continued rise and spread of drug-resistant pathogens, including carbapenem resistant (CR) strains of Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Methods This retrospective cohort analysis used real-world data from a large United States hospital-based database to examine the association between key clinical outcomes and different lengths of time to appropriate treatment between October 2010 and September 2015. Results Of 40,549 patients with GN-BSIs who were identified, 1117 (2.8%) had a CR GN-BSI. Overall, outcomes of hospitalized adult patients with GN-BSIs incrementally worsened the longer appropriate therapy was delayed. Patients with CR GN-BSIs had a median infection-associated length of stay (LOS) of 8, 9, 10, and 13 days, whereas patients with CS GN-BSIs had a median infection-associated LOS of 6, 7, 8, and 11 days for patients with days to appropriate therapy of 0, 1-2, 3-4, and ≥ 5 days, respectively. Among patients with CR GN-BSIs, the percentage of patients discharged home was 38%, 33%, 35%, and 31%, whereas in patients with CS GN-BSIs, the percentage of patients discharged home was 58%, 53%, 48%, and 43% for patients with days to appropriate therapy of 0, 1-2, 3-4, and ≥ 5 days, respectively. Conclusion The findings from this study highlight the clear need to deliver appropriate therapy more expeditiously in patients with CS and CR GN-BSIs.

Objective To estimate the incidence and recurrence of breast cancer (BC) in patients with vulvovaginal atrophy (VVA) treated with ospemifene and matched untreated VVA patients using real-world data. Study design Retrospective matched cohort study. Main Outcome Measures: VVA patients were identified from the 2011–2018 US MarketScan® insurance claims database. For incidence, ospemifene-treated VVA patients without evidence of BC prior to index treatment were matched to two untreated VVA controls similarly without history of BC on age, index VVA year, geographic region, Charlson Comorbidity categories, and follow-up time. BC after the index treatment was identified by BC diagnosis codes, mastectomy, chemotherapy, or radiation procedure. Incidence rate, rate ratio (RR) and their 95 % confidence intervals (CI) were calculated. The process was repeated to estimate BC recurrence in patients with a history of BC in 1:1, 1:2 and 1:3 matches. Results 1728 ospemifene users and 3456 untreated patients met the inclusion and matching criteria for assessing incidence. The average number of days for which ospemifene was supplied was 314 (standard deviation [SD] = 340). Average follow-up time from index treatment was 937 days (SD = 392) for treated patients and 915 days (SD = 396) for controls. BC incidence rates per 1000 person-years was 2.03 (95 % CI: 1.06−3.91) for treated patients and 3.53 (95 % CI: 2.49−4.99) for controls (RR = 0.58, 95 % CI: 0.28−1.21). No difference in recurrence was observed between ospemifene-treated and matched untreated patients. Ten (32.3 %) treated vs. 25 (40.3 %) controls in the 1:2 matched analysis had a recurrence. Conclusion No differences were observed in the BC incidence and recurrence rates in ospemifene users compared with matched controls.

Background Patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) have a poor prognosis, with a historic five-year overall survival (OS) of less than 10%. Patients with aNSCLC without common actionable oncogenic drivers such as EGFR mutations or ALK rearrangements are often limited to immunotherapy and/or chemotherapy, leaving a group of patients with unmet medical need. This study explored OS and progression-free survival based on radiographic imaging (PFS-I) among aNSCLC patients with EGFR wild type (wt) and ALK wt treated in real-world academic setting using AACR GENIE data. Methods Data collected from 4 academic cancer centers in North America from AACR Project GENIE cancer registry was used for this study. The data included patients who underwent next-generation genomic sequencing (NGS) between 2014 and 2017 linked with clinical outcomes obtained during routine practice. Patients initially diagnosed with stage III or IV aNSCLC, underwent NGS prior to or within 60 days after starting their first line of therapy (LOT1), with NGS-confirmed ALK wt and EGFR wt were selected. Patients were then classified into four groups based on their LOT1 regimen: chemotherapy single agent or combinations (chemo), immunotherapy-monotherapy (IO), targeted therapy (TT), and bevacizumab plus chemo (bev+chemo). PFS-I and OS were measured from the start of LOT1 for each therapy group. As progression data were only available for stage IV patients in AACR GENIE, PFS-I was reported for this subgroup only. Baseline characteristics were not adjusted. Results 263 patients satisfied criteria for inclusion in the study: 175 (67%), 31 (12%), 14 (5%), and 38 (14%) initiated chemo, IO, TT, and bev+chemo respectively. Of the 263 patients: 57% were female, mean age was 64, and 85% were current or former smoker. 99% of patients initiated LOT1 in year 2017 or earlier. 68%, 97%, 93%, and 100% were diagnosed with stage IV among chemo, IO, TT, and bev+chemo groups respectively. Median PFS-I (mPFS-I) in stage IV patients was 5.0 (confidence interval [CI]: 3.9-5.7) months, and median OS (mOS) in stage III/IV patients was 20.4 (CI:14.8-25.3) months. Among stage IV patients, mPFS-I by regimen group was 4.2 (CI:3.1-5.7), 4.0 (CI:1.4-7.1), 6.2 (CI:3.3-15.0), and 6.8 (CI:4.4-10.3) months for chemo, IO, TT, and bev+chemo respectively. Among stage III/IV patients, mOS by regimen group was 19.7 (CI:12.7-25.4), 18.4 (7.1-not reached [NR]), NR (CI:6.2-NR), and 23.5 (CI:10.3-35.1) months for chemo, IO monotherapy, TT, and bev+chemo respectively. Conclusion This is the first study to assess outcomes among aNSCLC patients who are EGFR-wt and ALK-wt from the AACR Project GENIE registry. It provides a descriptive assessment of clinical outcomes associated with standard care treatment in the academic setting as more treatment options become available. Citation Format: Hemanth Kanakamedala, Beilei Cai, Sara Bruce Wirta, Rohit Borker, Nydia Caro, Wen-Hsing Wu, Ariadna Holynskyj. Real-world clinical outcomes associated with first line treatments in patients with advanced non-small cell lung cancer without EGFR mutation or ALK rearrangement based on AACR GENIE [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 100.

Background Carbapenem-resistant Enterobacterales (CRE) are considered an urgent threat to human health by the CDC. Tracking resistance over time is of importance to understand trends and patterns. Tracking carbapenem resistance is complicated by definitions which include resistance to ertapenem only which can differ in epidemiology, mechanism, and treatment options. This study examines trends of CRE from 2015 to 2019 and the impact of carbapenem resistance on outcomes. Methods Enterobacterales infections identified in the Premiere HealthCare database from 2015 to 2019 were categorized into 3 groups: ertapenem only resistant (Erta-R); isolates resistant to ertapenem and class 2 carbapenems (CR-1/2); and carbapenem susceptible (CS). Trends in resistance over the study period were assessed. Furthermore, patient characteristics and outcomes were compared between groups. Results Among 225,457 unique cultures 692 were Erta-R, 2,397 were CRE-1/2, and 222,368 were CS. Overall rates of CRE-1/2 slightly increased from 0.9% to 1.2% over the study period (P for trend of < 0.0001) while there was a slight negative trend for Erta-R rates (P for trend =0.006). Rates of CR by pathogen (Figures 1 and 2) were relatively stable over the study period. Enterobacter cloacae was the most common organism in the Erta-R group and K. pneumoniae was the most common CRE-1/2 pathogen. Differences in patient characteristics were seen between the three groups for race, gender, and comorbidities (Table). Both mortality (Erta-R: 10%, CRE-1/2: 9% vs CS: 4%, respectively) and infection-associated length of stay (Erta-R: 8 days; CRE-1/2: 8 days vs CS: 6 days, respectively) were higher in both Erta-R and CRE 1/2 when compared to CS (P< 0.001). There were no differences in outcomes between patients with Erta-R and CRE 1/2. Figure 1. Annual rates of CRE (resistance to both classes) by pathogen over the study period Figure 2. Annual rates of CRE (ertapenem R only) by pathogen over the study period Table. Patient demographics and outcomes Conclusion CRE rates were relatively stable over the study period. Despite low incidence, CRE continue to have significant associations with morbidity and mortality. Interestingly, outcomes were similar in patients with isolates resistant to ertapenem only when compared to isolates resistant to both classes of carbapenems. This might be reflective of novel treatment options available over the study period. Disclosures Stephen Marcella, MD, Shionogi Inc. (Employee) Hemanth Kanakamedala, BS, Shionogi Inc. (Independent Contractor) Yun Zhou, MS, Shionogi Inc. (Independent Contractor) Bin Cai, MD, PhD, Shionogi Inc. (Employee) Jason M Pogue, PharmD, BCPS, BCIDP, Shionogi Inc. (Advisor or Review Panel member)

Background Treatment choices for carbapenem-resistant (CR) Acinetobacter baumannii infections are limited. We analyzed the impact of active treatment on outcomes in patients infected with CR vs carbapenem-susceptible (CS) A. baumannii. Methods Adult patients hospitalized between January 1, 2014 and June 30, 2019 with A. baumannii infections recorded in the Premier Database were retrospectively evaluated. Outcomes including mortality, discharge status (home vs other), and readmission rates were calculated as a function of receipt of active antibiotic treatment, infection site, and CR status. Antibiotic therapy was considered active if given after the index culture and displaying in vitro susceptibility. Results Among 3,500 patients with A. baumannii (CR n=1,608; CS n=1,892), 2,057 patients (58.8%) received active treatment, with a much lower proportion of CR A. baumannii patients receiving active treatment than CS patients (606 [37.7%] vs 1,451 [76.7%]). Patients without active treatment had similar rates of in-hospital mortality (14.3% vs 12.9%, P=0.25) but were less likely to be discharged to home (26.3% vs 37.0%, P< 0.001) than those that received active treatment. No association between receipt of active treatment and overall mortality or discharged status was demonstrated for CR isolates (Table 1). However, among the subset of patients with CR bloodstream infections, mortality was higher in those without active treatment compared to those with active treatment (55.1% vs 25.9%, P=0.009). Overall readmission rates due to A. baumannii were considerably higher for those who did not receive active treatment vs those who did (16.0% vs 7.5%, P< 0.001) and the same was seen by differing infection sites; primarily driven by CR patients with bloodstream, respiratory, or urine infections (Table 2). Table 1. Mortality and discharge status by active treatment and carbapenem susceptibility Table 2. Readmission due to A. baumannii by active treatment and CR status among patients discharged alive Conclusion Active antibiotic therapy was associated with improved outcomes in patients with A. baumannii infections, although perhaps not to the extent expected. Further investigation into the impact of active therapy on outcomes is warranted. Disclosures Jason M Pogue, PharmD, BCPS, BCIDP, Shionogi Inc. (Advisor or Review Panel member) Yun Zhou, MS, Shionogi Inc. (Independent Contractor) Hemanth Kanakamedala, BS, Shionogi Inc. (Independent Contractor) Bin Cai, MD, PhD, Shionogi Inc. (Employee)

e13048 Background: Neutropenia is the most common adverse event following administration of CDK4/6 inhibitors RIB and PAL for hormone receptor–positive (HR+) MBC. There are limited comparative real-world data on TE neutropenia in pts receiving these agents. Here we report incidence, duration, and severity data on TE neutropenia in such pts from an electronic health record dataset and administrative claims. Methods: This retrospective study comprised 2 mutually exclusive cohorts of pts with MBC receiving RIB or PAL. Pts were matched 1:1 based on age and year of treatment start. Prior baseline activity of ≥6 mo was required. The MarketScan claims databases was used to evaluate incidence rates of TE neutropenia from Jan 1, 2015, to Dec 31, 2018, in pts receiving RIB or PAL. Rate ratio was calculated using a Poisson model. Data on neutropenia severity and duration were obtained from Optum de-identified Electronic Health Record dataset. Neutropenia severity was defined by neutrophil counts from lab tests (grade 1/2, 1000- < 1500/μL; grade 3, 500- < 1000/μL; grade 4 < 500/μL) within the first 180 days of treatment. Neutropenia duration was estimated using Kaplan-Meier analysis and defined as the time between first abnormal neutrophil result and a lab result demonstrating neutropenia resolution. Results: After 1:1 matching, 152 pts from the MarketScan database were included in both the PAL and RIB cohorts; 168 matched pts were included from the Optum dataset. Neutropenia was reported in 38 pts (25%) in the PAL group and 25 pts (17%) in the RIB group. The rate of neutropenia per person–treatment year was 0.5 (95% CI, 0.4-0.7) in PAL pts vs 0.4 (95% CI, 0.3-0.6) in RIB pts. The rate ratio of neutropenia between treatments (PAL vs RIB) was 1.4 (95% CI, 0.8-2.3), which was not statistically significant, likely due to small sample size. Rates of neutropenia by severity with PAL vs RIB were 32% vs 32% for grade 1/2, 35% vs 26% for grade 3, and 4% vs 4% for grade 4, respectively. The rate ratio for grade 3 or grade 4 neutropenia (PAL vs RIB) was 1.3 (95% CI, 0.9-1.8). Median neutropenia duration was 29 vs 20 days ( P< .01) with PAL vs RIB. Conclusions: Treatment of HR+ MBC with RIB and PAL requires optimal management of TE neutropenia. Real-world data showed that pts with MBC receiving PAL had a numerically higher rate of neutropenia than pts receiving RIB. Rates of grade 3 neutropenia were higher with PAL vs RIB, and duration of neutropenia was longer with PAL vs RIB. Economic burden analyses of neutropenia will be presented.

Background: Sickle cell disease (SCD) is one of the most prevalent hemoglobinopathies in Lebanon, where 0.1% of the population are affected by the disease, with the highest prevalence in North Lebanon. SCD burden has not been well characterized in this patient population. Moreover, there is limited understanding of the factors associated with complications of SCD. We hereby report on characteristics, complications, treatments and survival of a SCD cohort treated at a comprehensive SCD referral clinic in North Lebanon. Methods: Data were extracted from the health records and electronic registry of 335 SCD patients treated at the comprehensive SCD clinic of Nini hospital, Tripoli, North Lebanon between 2009 and 2019. The study population consisted of referred and newly diagnosed patients. Patients were considered to be newly diagnosed with SCD if there was a gap of ≤ 60 days between SCD diagnosis date and their first clinic visit date. Patients were regularly seen in the clinic at intervals ranging from every 2 months to 1 year depending on their age and disease severity. Patient characteristics, complications, treatment choices, and mortality were evaluated during follow-up. Follow-up was defined as the time between SCD diagnosis and last visit to the clinic. Complications included vaso-occlusive crisis (VOC), acute splenic sequestration (ASS), stroke, dactylitis, joint necrosis, priapism, leg ulcers, sepsis, iron overload and mortality. VOC events, defined as the composite of pain and/or acute chest syndrome (ACS), were only reported if they resulted in a hospitalization. Since history of VOC events was not well documented among referred patients, VOC events were assessed among patients newly diagnosed at the clinic. Results: The mean age of the study population at SCD diagnosis was 2.9 years (standard deviation [SD]: 4.3), with 73.1% of patients diagnosed within 3 years of age. Mean age at first visit to the clinic was 8.6 years (SD 10.0). 159 (47.5%) patients were female. The most common genotypes were Hemoglobin SS (233 [69.6%]), Hemoglobin Beta-0 Thalassemia (62 [18.5%]), and Hemoglobin Beta + thalassemia (27 [8.1%]). The mean number of follow up years between SCD diagnosis date and latest visit date to the clinic was 13.7 (SD: 10.5). 132 (39.4%) patients were newly diagnosed at the time of their first visit to the clinic. The most frequently encountered SCD clinical events were pain (189 [56.4%]) followed by ACS (135 [40.3%]), ASS (115 [34.3%]) and joint necrosis (55 [16.4%]). The incidence of stroke, pulmonary hypertension, priapism, leg ulcers and sepsis was low (3.3%, 4.2%, 6.0%, 3.0% and 3.9%). Persistent splenomegaly beyond 6 years was seen in 57 (17%) patients, 36 (63.2%) of these patients were of SS genotype. 276 (82.4%) patients required at least one hospitalization during their follow-up. Among newly diagnosed patients, 63% experienced at least one VOC event that led to a hospitalization with a mean of 0.4 (SD: 0.6) hospitalized VOC events per patient per year. 15 (4.5%) patients died during follow-up. The most common cause of death was stroke (3 [20%]). 84 (25.1%) and 76 (22.7%) patients underwent a cholecystectomy and surgical splenectomy respectively, and 30 (9.0%) patients underwent both. 236 (70.5%) patients were treated with Hydroxyurea. The mean age at introduction of Hydroxyurea was 11.5 years (SD: 10.1) and median starting dose was 15.2 mgs/kg/day. 281 (84%) patients received at least one blood transfusion during their follow-up. 37 (11.0%) patients received iron chelation during their follow up. 3 (0.9%) patients underwent bone marrow transplant and were cured of their disease. Conclusion: This first SCD study from North Lebanon demonstrates that SCD burden in North Lebanon is significant. Despite the high disease burden and the low community resources in this region, survival rate of this SCD patient population is relatively high. This can be attributed to the young age at diagnosis, the close comprehensive follow-up and the regular parent/patient education. The low rate of stroke, priapism and leg ulcers in this population warrants further investigation via disease associated markers and genetic determinants. As for priapism, it may be underreported due to social stigma in a conservative country as Lebanon. Noteworthy, Iron overload is under recognized and sub optimally treated. The association between specific risk factors and disease complications will be further addressed. Disclosures Inati: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novonordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding; Global Blood Therapeutics: Research Funding. Kanakamedala:Novartis: Consultancy; Genesis Research: Employment. Pilipovic:Novartis Pharma AG: Employment, Equity Ownership. Sabah:Novartis: Employment.

Background Urinary tract infections (UTIs) are the most frequent infections caused by Gram-negative (GNB) bacteria in the USA. We aimed to characterize the burden of UTIs caused by carbapenem-resistant (CR) or -susceptible (CS) GNB in hospitalized patients with or without bacteremia. Methods Data from the Premier Healthcare Database of adult patients hospitalized between January 1, 2014 and June 30, 2018 with UTIs (defined as positive urine culture and receipt of GN antibiotics within −2 to 3 days of the index urine culture) with bacteremia (defined as positive blood culture with the same pathogen from the urine) or without bacteremia caused by CR or CS GNB were analyzed retrospectively. Stenotrophomonas maltophilia were presumed to be CR but rarely tested. Patient characteristics and outcomes (mortality, different types of length of hospital stay [LOS], ICU admission, discharge status and hospitalization charges) were compared. Results A total of 46,076 UTI patients were included. 11,212 patients with bacteremia were significantly more likely to have UTI index culture on the day of the admission vs. 34,864 patients without bacteremia (82.0% vs. 65.9%, P < 0.001, respectively). The same results were seen when stratified by CR status (CR: 68.59% vs. 61.23%, P < 0.047; CS: 82.29% vs. 66.19%, P < 0.001, respectively). UTI patients with bacteremia were also more likely to have a positive blood culture for the same pathogen on the same day of index urine culture (CR: 85.86%; CS: 95.45%). Pseudomonas aeruginosa was the most frequent CR pathogen (50.03%), followed by K. pneumoniae (14.28%) and Stenotrophomonas maltophilia (10.76%), and CR patients with bacteremia were more likely to die in the hospital and less likely to be discharged home than other groups. They also had longer median overall and infection-associated LOS, were more likely to be admitted to the ICU and had higher hospitalization charges (table). Conclusion UTIs complicated by bacteremia exacerbates the burden of illness in patients hospitalized with UTIs, increasing mortality, LOS, and hospitalization charges. The presence of CR pathogens further exacerbates this burden. Disclosures All authors: No reported disclosures.

Background Infections caused by Acinetobacter baumannii present a challenge for treating physicians due to the high level of antimicrobial resistance. The current analysis compared the burden of illness in patients infected with carbapenem-resistant (CR) vs. -susceptible (CS) strains of A. baumannii. Methods Hospitalized adult patients with microbiologically confirmed A. baumannii infections (defined as a positive culture and receipt of antibiotics between 2 days prior to 3 days after the culture) included in the Premier Healthcare Database were retrospectively evaluated. Patient characteristics including demographics, comorbidities, time of infection onset and site of infection were assessed. Comparative outcomes between CR and CS patients assessed included in-hospital mortality, length of hospital stay (LOS), ICU LOS, and discharge status. Outcomes were also stratified by site of infection. Results A total of 3,471 patients admitted between January 1, 2014 and June 30, 2018 were included. Patients with CR strains of A. baumannii were older (62 vs. 59 years), more likely to have Charlson Comorbidity Index ≥3 (63.4% vs. 56.1%), more likely admitted from a healthcare origin (30.3% vs. 11.4%) and less likely to have the onset of infection within first 48 hours of hospitalization (58% vs. 69%) than those with CS strains. CR patients had increased inpatient mortality compared with CS patients (16.3% vs. 11.0%), driven primarily by patients with bloodstream infections (42.6% vs. 12.4%, respectively, P < 0.001). CR patients had a non-significantly increased median overall LOS from the onset of infection (9 vs. 8 days, P = 0.068), were more likely to be admitted to the ICU, and were significantly less likely to be discharged home (16% vs. 47%, P < 0.001). Hospitalization charges were considerably higher for CR patients (table). Readmission rates were high among CR patients and were similar to patients with CS infections. Conclusion Patients with CR strains of A. baumannii face a greater burden of illness compared with CS patients, experiencing increased mortality, ICU admission and LOS, and incur higher hospitalization charges. Furthermore, CR patients were less likely to be discharged home after admission. Disclosures All authors: No reported disclosures.

Background The deleterious outcomes associated with delay receipt of appropriate therapy are well documented. However, scant data exists on the consequences of each day delay of appropriate therapy and subsequent outcomes among adult hospitalized patients with GN-BSIs. Methods Study design: a retrospective cohort analysis. Study population: consecutive adult, hospitalized patients with a GN-BSI (11 most prevalent pathogens) in 1 of 181 institutions contributing microbiology data to the Premier Healthcare Database (October 2010–Sep 2015). Exclusion criteria: age < 18 years; diagnosis of pregnancy or cystic fibrosis, died or discharged within 2 days of index GN-BSI culture, lack of sufficient antibiotic susceptibility or treatment data to determine appropriateness. Day of initiating appropriate therapy was defined as the first day when the patient received an antibiotic with in vitro activity against the GN-BSI post index culture. Results were summarized by Kaplan–Meier estimates, and Cox Proportional-Hazards (CPH) analyses modeling discharge to home were conducted. Time to initiate appropriate therapy (0, 1–2 days, 3–4 days, ≥5 days) was included in the CPH model as an ordinal variable. Results A total of 40,549 patients met selection criteria. Mean (SD) age was 67.5 (16.1) years and 54% were female. E. coli and K. pneumoniae were the most common GN-BSI (58.0% and 18.3%, respectively). Approximately 30% of patients were in the ICU at index GN-BSI and in-hospital mortality was 6.8%. The mean (SD) time to receive appropriate therapy post index GN-BSI culture was 0.6 (2.7) days, and 69.7%, 22.5%, 5.7% and 2.1% received appropriate therapy in 0, 1–2, 3–4, and ≥5 days of index GN-BSI, respectively. The mean/median LOS post index GN-BSI by 0, 1–2, 3–4, and ≥5 days delays in appropriate treatment were 8.3/6, 9.8/7, 11.5/8, and 19.2/11 days respectively. Kaplan–Meier plots are shown in Figure 1. In the CPH model, each interval delay in appropriate therapy was associated with a 21% decrease in the likelihood of being discharged home for patients with GB-BSIs. Conclusion Hospital length of stay was found to increase when appropriate therapy was delayed. These findings highlight the critical need for early appropriate therapy among patients with GN-BSIs. Disclosures All authors: No reported disclosures.

Background The deleterious consequences of BSIs due to CR-GN bacteria among hospitalized adult patients are well described in the literature. However, scant data exist that compares the baseline features and outcomes of patients with CR-GN-BSIs due to LFs relative to those caused by NLFs. Methods We performed a retrospective cohort analysis of consecutive hospitalized adult patients (age ≥18 years) in the Premier Healthcare Database (January 2014–June 2018) with GN-BSI due to select LFs (E. coli, Klebsiella spp., Citrobacter spp., Enterobacter spp., and Serratia spp.) and NLFs (Pseudomonas spp., Acinetobacter spp., and Stenotrophomonas spp.). Patients with a diagnosis of cystic fibrosis or who had both LF and NLF GNB on index BSI culture were excluded. Baseline demographics, medical history, comorbidities, hospitalization history, and outcomes were compared between patients with CR-GNB due to LFs and NLFs. Outcomes assessed included composite death (in-hospital death or discharge to hospice), in-hospital mortality, discharge to home, and hospital length of stay post index GNB-BSI culture collection. Results Of the 1749 patients with a CR-GNB-BSI due to an LF or NLF, 1505 met study criteria. Of the 1505, 418 (27.8%) were LFs and 1087 (72.2%) were NLFs. The most common LFs were Klebsiella spp. (55.7%) and Enterobacter spp. (25.7%), while Stenotrophomonas spp. (45.2%) was the most common NLF. Overall, groups were highly similar at baseline but patients with CR-GNB-BSIs due to an LF were slightly older and more likely to be in the ICU at index BSI culture collection (table). Outcomes were also comparable between patients with CR-GNB-BSIs due to LFs and NLFs but there were a few notable differences. Composite mortality was higher in patients with GNB-BSIs due to an LF and these patients were also less likely to be discharged home. Conclusion The findings indicate that CR-GNB-BSIs result in considerable morbidity and mortality irrespective of whether the GNB is an LF or NLF. One in five patients died during their hospitalization and less than half were discharged home. This highlights the need for better and more preventive and therapeutic strategies aimed at combating CR-GNB-BSIs. Disclosures All authors: No reported disclosures.

112 Background: Reducing hospitalizations for chemotherapy-related toxicities represents an opportunity to improve both the quality and cost of cancer treatment. Nausea and vomiting (NV) account for almost 10% of “avoidable” toxicity-related post-chemotherapy hospitalizations (2016 Medicare data). We sought to evaluate the event cost of NV-related hospitalizations among patients with cancer from a US payer perspective. Methods: From a large US claims database (Truven MarketScan), we identified hospitalizations with NV as the primary diagnosis and cancer as a secondary diagnosis (01/2011-06/2017). This method increases specificity for NV as the principal hospitalization factor, while underreporting the prevalence of NV as a contributory factor. To determine event costs, we evaluated hospital and other reimbursement during the hospitalization. To explore subgroup differences, we stratified results by tumor type, payer type, admission route, receipt of highly emetogenic chemotherapy (HEC; 2017 definition includes carboplatin AUC ≥4) and antiemetic prophylaxis. We adjusted all costs to 2017 US dollars. Results: Among 918,192 hospitalizations involving cancer, we identified 80,995 with both NV and a cancer diagnosis code. Of these, 5,293 had NV as the primary diagnosis and 62 lacked cost data. Patients (mean age = 57.7±16.2) were 67% female. Median hospital length of stay was 4 days and mean cost per hospitalization was $15,085. Non-Medicare admissions (82%) had a higher mean cost vs. Medicare ($15,737 vs. $12,111, p < 0.01). We found < $1,000 difference between the highest and lowest cost per hospitalization among the 6 most common tumor types. We found the 65% of patients with a chemotherapy claim ≤30 days prior to hospitalization had costs of $13,882 per event. Among the 45% of chemotherapies that were HEC, > 50% lacked an NK1 receptor antagonist as prophylaxis. Conclusions: The average cost of NV-related hospitalizations among patients with cancer exceeds $15,000 per event, highlighting the need to effectively address this symptom. Roughly half the hospitalizations involved HEC, with over half of those patients not receiving guideline-based antiemetic prophylaxis.