bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing proven methods in a community-based health system to improve breast cancer screening rates during the COVID-19 pandemic.
Authors: Fadel Celine , Danak Shivang , Caton Andria P 
Published: June 2022

6565 Background: There are reduced screening rates across the United States secondary to the COVID-19 pandemic; the additional anticipated deaths from breast and colorectal cancer, secondary to reduced screening, is approximated at 10,000 people. A study of thirty-two health systems in Georgia noted an 8% decrease in screening mammography compared to pre-pandemic rates. To help reverse the decline, Northeast Georgia Medical Center (NGMC) participated in the "Return to Screening" initiative, in conjunction with the American Cancer Society (ACS). A quality improvement project was performed at the community-based hospital system to increase breast cancer screening rates, using a multidisciplinary approach with a focus on health care disparities. Methods: The initial goal was to increase screening mammograms by 10% (n = 14,364) from June 1st to December 1st 2021. Interventions were selected by a multidisciplinary team of NGMC researchers, clinical providers, and oncology administrators. Interventions varied in category, encompassing unique patient and provider-specific approaches. The evidence-based interventions were tailored to address health care disparities in the local population. This included identification and quantification of cultural groups in the community to ensure quality patient access. Integrative collaboration consisted of intermittent meetings to certify consistent communication, project reflection and identification of barriers. The selected interventions were executed monthly, with simultaneous data tracking of mammography rates. Results: From June 1st to December 1st 2021, a total of forty evidence-based interventions were successfully implemented. Analysis of screening rates demonstrated a 15% increase across the allotted time period, corresponding to an average of 1,302 mammograms monthly (n = 15,284). This exceeded the initial anticipated goal of increasing screening by 10% (n = 14,364). Analysis of mammography results identified 331 new cases of breast cancer diagnosed within the allotted period, a 7% mean diagnosis rate increase. Certain planned interventions were unable to be conducted and required modification due to limitation of the ongoing pandemic; however, this solidified the use of social media and virtual participation as effective methods of community outreach. Conclusions: We identified key methods to engage the local community and successfully increased rates of screening mammography. Interventions were tailored to the local population, ensuring patient-centered tools and a personalized approach to medicine. The multidisciplinary, consistent collaboration with stakeholders ensured quality of care for the local patient population. This project demonstrates the importance of local community engagement to impact national cancer screening rates, and thus, ensure earlier detection of breast cancer.
Overall survival (OS) of patients with TRK fusion–positive cancer receiving larotrectinib versus standard of care (SoC): A matching-adjusted indirect comparison (MAIC) using real-world data (RWD).
Authors: Bokemeyer Carsten , Paracha Noman , Lassen Ulrik Niels , Italiano Antoine , Sullivan Sean D , Marian Marisca , Fellous Marc Mardoche , García-Foncillas Jesús 
Published: June 2022

6579 Background: Larotrectinib trials in Tropomyosin Receptor Kinase (TRK) fusion cancer population were single arm trials and therefore limited comparative effectiveness data with larotrectinib are available.MAIC is typically used to balance population characteristics to facilitate cross-study comparisons. The objective of this study was to use MAIC to compare efficacy of the highly specific TRK inhibitor larotrectinib vs. SoC. Methods: Individual patient data from larotrectinib trials (NCT02122913, NCT02637687, NCT02576431) were compared with published aggregate SoC data from patients with locally advanced/metastatic TRK fusion cancer identified in the Flatiron Health/Foundation Medicine clinico-genomic database (Demetri et al. Ann Oncol. 2021). Prior to matching, eligible patients were ≥18 years and had to have received ≤4 lines of prior therapy (LoPT). Patients were matched on available common baseline characteristics (Table). Overall survival was the only endpoint assessed and was defined as time from locally advanced/metastatic disease diagnosis to death. The analyses included: 1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and 2) estimation of treatment effect of larotrectinib vs. SoC. Hazard ratios (HRs) were used to compare the 2 groups. MAIC assumes that all observed and unobserved prognostic factors are adjusted for in the analysis. Results: 85 larotrectinib patients and 28 SoC patients were included. After matching, log-rank testing suggested no difference between the 2 groups (P=0.26), and larotrectinib was associated with a 78% lower risk of death (adjusted HR: 0.22 [95% confidence interval: 0.09, 0.54]; P=0.001), compared to SoC. Conclusions: This analysis suggests longer overall survival with larotrectinib, compared to SoC, in adult patients with TRK fusion cancer. The current analysis was limited to the prognostic variables available in the RWD. Further data are warranted to confirm those results. [Table: see text]
Frailty status derived from the electronic medical record to predict survival and health care utilization in veterans with lung and gastrointestinal cancers.
Authors: Yarlagadda Sudha , Razjouyan Javad , Naik Aanand , Sada Yvonne 
Published: June 2022

6582 Background: Frailty is associated with increased vulnerability to stressors. Although frailty is a predictor of survival, traditional frailty assessments are not feasible in clinical practice. Frailty indexes (FI) derived from the electronic medical record (EMR) are an alternate approach. There is limited data for the association between EMR-FI and cancer-related outcomes including survival and health care utilization. Methods: We identified a cohort of patients diagnosed with lung or gastrointestinal cancer from 2016-2020 using VA administrative files. We used the Veterans Affairs-FI (VA-FI), a validated 31-item cumulative deficit FI, to define three groups: robust (≤0.1), prefrail (0.1-0.2), frail ( > 0.2). Cox proportional hazard analyses were conducted to evaluate survival. Logistic regression analyses were performed to examine healthcare utilization. All models were adjusted for age, gender, race, Charlson comorbidity index, and stage. Results: Among 37,439 patients (age: 70±8.6 years), the majority were prefrail (36.8%) or frail (24.1%). Prefrail patients had a 13% increased risk of death compared to robust patients (adjusted hazard ratio [aHR] 1.13; 95% CI 1.10-1.16), while frail patients had a 52% increased risk (aHR 1.52; 95% CI 1.47, 1.57). Pre-frail and frail patients had increased odds of 1-year ED visits (adjusted odds ratio [aOR] 1.33; 95% CI 1.27 - 1.40 and aOR, 1.88, 95% CI 1.77-2.00, respectively). Frailty status was associated with increased odds of 1-year all-cause hospitalization among prefrail (aOR 1.09; 95% CI 1.03-1.15) and frail patients (aOR 1.26; 95%CI: 1.18, 1.34). Conclusions: Frailty measured by EMR data is significantly associated with survival and healthcare utilization among patients with lung and gastrointestinal cancers, independent of stage. Further study is warranted to develop EMR-FI as a risk stratification tool for personalized cancer treatment decisions.
Price variability of pembrolizumab in New York City from 2016-2021.
Authors: Hussaini Syed , Johnson Jordan , Chino Fumiko 
Published: June 2022

6601 Background: There is poor compliance among cancer centers with price transparency rules set forth by the CMS in 2021. Service charges higher than what a hospital reasonably expects to be reimbursed may both prevent competitive price shopping by the consumer and result in catastrophic financial toxicity for small payors and under/uninsured individuals. We investigated variability in the charged and reimbursed payments for pembrolizumab infusion within one metro area utilizing Medicare claims. Methods: Medicare claims data from 2016 through 2021 for all pembrolizumab (HCPCS J9271) infusions in a hospital outpatient department were selected from the Definitive Healthcare claims database for medical oncology providers in New York City (NYC). Average charges, reimbursements, and total claims were obtained for the 6 largest prescribers by volume. Annual percentage changes (APC) were calculated to evaluate trends during study period. Prices are presented as inflation adjusted numbers (charged and reimbursed; 2021 dollars). Analyses were performed in Excel (Microsoft Corp). Results: Our analysis included 5 NCI-designated cancer centers (NCI-A, NCI-B, NCI-C, NCI-D) of which 1 was PPS (Prospective Payment System)-exempt (NCI-PPS). One hospital was non-NCI and 4 hospitals were part of the discounted 340B Drug Pricing Program (NCI-A, NCI-B, NCI-D, Non-NCI). From 2016 to 2021, total Medicare claims increased 793 to 1537, and total payments to all centers increased from $5.4M to $16.3M. NCI-PPS comprised 61% of claims, and 65% of total payments in 2021. Average charge for pembrolizumab in 2021 ranged from $20,130 (NCI-PPS) to $155,825 (NCI-D/340B). During study period, APC ranged from +1.7% (NCI-A/340B) to +25.4% (NCI-D/340B). Despite wide variability in charged amounts for Medicare claims, re-imbursed amounts were similar across centers (range: $6227-9623, 2021). Conclusions: There is significant variability in charges for pembrolizumab in Medicare claims with price increases outpacing the annual rate of inflation. Within NYC, the highest charges were from a 340B hospital; NCI-PPS had higher volume and total payments but consistently lower charged prices each year. Our study highlights extreme price variability, and has policy implications for price transparency requirements and uniform rate setting to establish payment levels and control rate of annual growth. [Table: see text]
MOMENTUM: Phase 3 randomized study of momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor.
Authors: Mesa Ruben A. , Gerds Aaron Thomas , Vannucchi Alessandro , Al-Ali Haifa Kathrin , Lavie David , Kuykendall Andrew T. , Grosicki Sebastian , Iurlo Alessandra , Goh Yeow Tee , Lazaroiu Mihaela Cornelia , Egyed Miklos , Fox Maria Laura , McLornan Donal P. , Perkins Andrew , Yoon Sung-Soo , Gupta Vikas , Kiladjian Jean-Jacques , Donahue Rafe , Kawashima Jun , Verstovsek Srdan 
Published: June 2022

7002 Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials. This pivotal phase 3 study of MF patients (pts) previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and spleen volume endpoints at 24 weeks (wks). Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb <10 g/dL; prior JAKi for ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 wks or Gr 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm. Stratification: TSS, palpable spleen, and RBC units transfused. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks, after which pts could receive open-label MMB. Assessments: Pt reported symptoms using a daily eDiary and spleen volume by MRI or CT. The primary endpoint was TSS response (≥50% reduction from baseline [BL]) rate at wk 24. Secondary endpoints, assessed sequentially at wk 24, were RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 94 of 130 (72%) MMB pts and 38 of 65 (58%) DAN pts completed the 24-wk randomized treatment (RT) phase. Median BL TSS were 28 (MMB) and 26 (DAN), Hgb were 8.1 (MMB) and 7.9 (DAN) g/dL, and platelets were 97 (MMB) and 94 (DAN) x109/L. BL TI was 13% (MMB) and 15% (DAN). Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%). All primary and key secondary endpoints were met (Table). Most common Gr ≥3 TEAEs in the RT phase of the study were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). Gr ≥3 infections occurred in 15% of MMB and 17% of DAN pts. Peripheral neuropathy occurred in 5 (4%) of MMB (all Gr ≤2) and 1 (2%) of DAN (Gr ≤2) pts in the RT phase, and none discontinued study drug. Overall, TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN (HR=0.506, p=0.0719). Conclusions: In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia. Clinical trial information: NCT04173494. [Table: see text]
V-FAST master trial: Preliminary results of treatment with CPX-351 plus midostaurin in adults with newly diagnosed FLT3-mutated acute myeloid leukemia.
Authors: McCloskey James K. , Pullarkat Vinod A. , Mannis Gabriel N. , Lin Tara L. , Strickland Stephen Anthony , Fathi Amir Tahmasb , Erba Harry Paul , Faderl Stefan , Chakravarthy Divya , Lutska Yana , Chandrasekaran Vijayalakshmi , Cheung Ronald , Levis Mark J. 
Published: June 2022

7043 Background: CPX-351 (US: Vyxeos; Europe: Vyxeos liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved for newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes in patients aged ≥1 year in the US and in adults in Europe. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 significantly improved overall survival and remission rates versus conventional 7+3, with a comparable safety profile. Preclinical data suggest CPX-351 may have synergistic activity with targeted agents, including the FLT3 inhibitor midostaurin (MID). Herein, we report preliminary results for the cohort of adults treated with CPX-351 + MID in the V-FAST (Vyxeos – First Phase Assessment with Targeted Agents) trial. Methods: V-FAST is an open-label, multicenter, multiarm, nonrandomized, phase 1b master trial (NCT04075747) to evaluate the safety and preliminary efficacy of CPX-351 combined with targeted agents (midostaurin, venetoclax, enasidenib). Eligible adults in the CPX-351 + MID cohort were aged 18 to 75 years, had newly diagnosed AML with a FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation, were fit for intensive chemotherapy, and had an ECOG performance status of 0 to 2. The dose-exploration phase (3+3 design) determined a recommended phase 2 dose of CPX-351 100 units/m2 (daunorubicin 44 mg/m2 + cytarabine 100 mg/m2) on Days 1, 3, and 5 + MID 50 mg BID on Days 8 to 21. There were no dose-limiting toxicities, and additional patients were enrolled in the expansion phase at this dose. Results: A total of 23 patients received CPX-351 + MID and had sufficient data to be included in the analysis (cutoff date: 1/20/2022). Patient baseline characteristics are shown in the Table. Treatment-emergent adverse events (TEAEs) in ≥40% of patients included febrile neutropenia (78%), nausea (65%), increased alanine aminotransferase (57%), leukopenia (57%), thrombocytopenia (57%), headache (43%), and hyponatremia (43%). All patients experienced a grade 3/4 TEAE, primarily hematologic events. Nonhematologic grade 3/4 TEAEs in ≥2 patients included pneumonia (17%), lung infection (13%), and hyperglycemia (9%). There were no grade 5 TEAEs and no deaths on or before Day 60. Complete remission was achieved by 18/22 (82%) evaluable patients after the first induction cycle. Conclusions: Preliminary results from the V-FAST trial suggest CPX-351 + MID is feasible, with a manageable safety profile and promising remission rates in adults with newly diagnosed AML who have a FLT3 mutation. Clinical trial information: NCT04075747. [Table: see text]
ASPEN: Long-term follow-up results of a phase 3 randomized trial of zanubrutinib (ZANU) versus ibrutinib (IBR) in patients with Waldenström macroglobulinemia (WM).
Authors: Tam Constantine Si Lun , Garcia-Sanz Ramón , Opat Stephen , D'Sa Shirley , Jurczak Wojciech , Lee Hui-Peng , Cull Gavin , Owen Roger G. , Marlton Paula , Wahlin Bjorn E. , Tedeschi Alessandra , Castillo Jorge J. , Siddiqi Tanya , Buske Christian , Leblond Veronique , Chan Wai Y. , Schneider Jingjing , Cohen Aileen , Huang Jane , Dimopoulos Meletios A. 
Published: June 2022

7521 Background: ASPEN is a randomized, open-label, phase 3 study comparing ZANU, a potent and selective Bruton tyrosine kinase inhibitor (BTKi), with the first-generation BTKi IBR in patients with WM. We present data with a median follow-up of 43 months. Methods: Patients with MYD88 mutations were assigned to cohort 1 and randomized 1:1 to receive ZANU 160 mg twice daily or IBR 420 mg once daily. Randomization was stratified by CXCR4 mutational status and lines of prior therapy (0 vs 1-3 vs > 3). Patients without MYD88 mutations were assigned to cohort 2 and received ZANU 160 mg twice daily. The primary endpoint was proportion of patients achieving complete response or very good partial response (CR+VGPR). Results: A total of 201 patients (ZANU arm, n = 102; IBR arm, n = 99) were enrolled in cohort 1 and 28 patients were enrolled in cohort 2. A larger proportion of patients in the ZANU arm of cohort 1 vs IBR had CXCR4 mutations by next-generation sequencing (32% vs 20%, or 33 of 98 vs 20 of 92 with data available) and were aged > 75 years (33% vs 22%). Median duration of treatment was 42 months (ZANU) and 41 months (IBR), with 67% and 58% remaining on treatment, respectively. The CR+VGPR rate by investigator was 36% with ZANU vs 22% with IBR ( p= 0.02) in cohort 1, and 31% in cohort 2. One patient achieved CR (cohort 2). In patients with wild type or mutant CXCR4 from cohort 1, CR+VGPR rates with ZANU vs IBR were 45% vs 28% ( p= 0.04) and 21% vs 5% ( p= 0.15) , respectively. Median progression-free survival and overall survival were not yet reached. Rates of atrial fibrillation, diarrhea, hypertension, localized infection, hemorrhage, muscle spasms, pneumonia, and adverse events leading to discontinuation or death were lower with ZANU vs IBR (Table). Exposure-adjusted incidence rates of atrial fibrillation/flutter and hypertension were lower with ZANU vs IBR (0.2 vs 0.8 and 0.5 vs 1.0 persons per 100 person-months, respectively; p< 0.05). Rate of neutropenia was higher and rate of grade ≥3 infection was lower with ZANU vs IBR. Safety outcomes of ZANU were similar between cohorts 1 and 2. Conclusions: ASPEN is the largest phase 3 trial with head-to-head BTKi comparison in WM. At a median follow-up of 43 months, ZANU was associated with higher CR+VGPR rate and demonstrated clinically meaningful advantages in long-term safety and tolerability vs IBR. Clinical trial information: NCT03053440. [Table: see text]
Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: Five-year follow-up of ELEVATE-TN.
Authors: Sharman Jeff Porter , Egyed Miklos , Jurczak Wojciech , Skarbnik Alan P. , Kamdar Manali K. , Munir Talha , Fogliatto Laura , Herishanu Yair , Banerji Versha , Follows George , Walker Patricia , Karlsson Karin , Ghia Paolo , Janssens Ann , Ferrant Emmanuelle , Munugalavadla Veerendra , Yu Ting , Wang Min Hui , Woyach Jennifer Ann 
Published: June 2022

7539 Background: For ELEVATE-TN (NCT02475681), we previously reported superior efficacy of acalabrutinib (A) ± obinutuzumab (O) vs O + chlorambucil (Clb) in patients (pts) with treatment-naive (TN) chronic lymphocytic leukemia (CLL) at 28.3 and 46.9 months (mo) median follow-up. Now, we report results from a 5-y update. Methods: Pts were randomized to A+O, A, or O+Clb. Pts who progressed on O+Clb could cross over to A monotherapy. Investigator-assessed (INV) progression-free survival (PFS), INV overall response rate (ORR), overall survival (OS), and safety were evaluated. Results: A total of 535 pts (A+O, n=179; A, n=179; O+Clb, n=177) had a median age of 70 y. At a median follow-up of 58.2 mo (range, 0.0–72.0; data cutoff Oct 1, 2021), median PFS was not reached (NR) (hazard ratio [HR]: 0.11) for A+O and A (HR: 0.21) vs 27.8 mo for O+Clb (both P<0.0001). Estimated 60-mo PFS rates were 84% (A+O), 72% (A), and 21% (O+Clb). Median OS was NR in any treatment arm, and significantly longer in the A+O vs O+Clb arms (HR: 0.55; P=0.0474); estimated 60-mo OS rates were 90% (A+O), 84% (A), and 82% (O+Clb). ORR was significantly higher with A+O (96%; 95% CI 92–98) and A (90%; 85–94) vs O+Clb (83%; 77–88; P<0.0001 [A+O], P=0.0499 [A]). Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were higher with A+O (29%/3%) vs O+Clb (13%/1%); 13%/1% had CR/CRi with A; CR increased since the interim analysis (previously 21% [A+O] and 7% [A]). Adverse events (AEs) and treatment exposure are shown in the Table. Treatment is ongoing in 65% (A+O) and 60% (A) of pts; the most common reasons for treatment discontinuation were AEs (17% [A+O], 16% [A], 14% [O+Clb]) and progressive disease (6%, 10%, 2%, respectively). Crossover from O+Clb to A occurred in 72 (41%) patients; 25% of these pts discontinued A (10% due to AEs and 11% due to progressive disease). Conclusions: After a 5-y follow-up, efficacy and safety of A+O and A monotherapy were maintained, with significantly longer OS in the A+O arm compared with O+Clb. Clinical trial information: NCT02475681. [Table: see text]