bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of switching to S-1 after other fluoropyrimidine-related cardiotoxicity during chemotherapy for solid tumors.
Authors: Osterlund Pia J. , Kinos Sampsa , Halonen Päivi , Soveri Leena-Maija , Kwakman Johannes J , Salminen Tapio , McDermott Raymond S. , Pfeiffer Per , Heervä Eetu , Liposits Gabor , Röckert Rebecka , Ålgars Annika , Kallio Raija S. , Sorbye Halfdan , Flygare Petra , Hagman Helga , Shah Carl-Henrik A. , van Werkhoven Erik D. , Glimelius Bengt , Punt Cornelis J. A. ,   Cardioswitch Group
Published: May 2020

7037 Background: Fluoropyrimidines (FP) are the cornerstone of chemotherapy in many solid tumors and linked to cardiotoxicity (CarTx) in about 5% (Polk, Cancer Treat Rev 2013), often leading to FP discontinuation. CarTx may be less common with S-1 and successful switch from other FP has been reported (Kwakman, EJC 2017). Methods: This 6-country, 12-center, cohort study included patients with solid tumors (ICD10 C15-C21, C24-25, C50, C80) who experienced FP-related CarTx. Primary endpoint was recurrent (R) CarTx during S-1 therapy after switch from any other FP. Results: CarTx during capecitabine (n = 124), continuous (n = 13) or bolus 5-fluorouracil (n = 4) was reported for 141 patients who switched to S-1 therapy. CarTx was chest pain including vasospasm without cardiac findings (55%), acute coronary syndrome or myocardial infarction (32%), atrial fibrillation (4%), heart failure/cardiomyopathy (4%), tachy-/bradycardia (3%), and/or other (15%). CarTx was grade 3-4 in 55%, appeared on cycle 1-2 in 89%, and at median 4 days (range 0-466) from FP initiation (Table). Causality was judged related in 26%, probable in 60%, and possible in 14%. Action with FP causing CarTx was permanent discontinuation in 91%. Treatment intent was curative in 70%. Cumulative incidence of RCarTx with S-1 was 3.5% (CI95%, 1.2-8.4%) and median time to R-CarTx was 11 (range 6-195) days. Four (out of 141) had grade 1 and one grade 2 R-CarTx. Three were judged possibly related to S-1 and 2 not related. S-1 was discontinued in one patient and continued in 4 (for 63-252 days) without action (n = 2), with dose reduction (n = 1), or delay (n = 1). There were no differences in demographic or risk factors regarding R-CarTx on S-1 (Table). Conclusions: FP-related CarTx is often severe, occurs early, and leads to permanent FP discontinuation. Switching to S-1-based therapy is safe, with, at the most, grade 1-2 R-CarTx in only 3.5%, and rarely leads to treatment discontinuation (0.7%), allowing patients to continue on an FP-based regimen. Clinical trial information: NCT04260269 . [Table: see text]
Implementing routine patient-reported outcome collection in a large, academic health system.
Authors: Shah Nishant , Wojcieszynski Andrzej , Davis Erin , Braun Jennifer , Garrett Meg , Shulman Lawrence N. , Metz James M. , Gabriel Peter Edward 
Published: May 2020

7053 Background: Patients' symptoms and side effects have traditionally been assessed by clinicians. There is increasing evidence that patient self-reported symptom severity often differs from clinician assessment, and that collecting patient-reported outcomes (PRO) can improve communication, symptom management, and even survival. However, the implementation of routine PRO collection across a large healthcare system poses operational and informatics challenges. Methods: Using native electronic health record (EHR) functionality, we implemented a standardized PRO questionnaire across a large academic cancer center and associated community-based practices. The questionnaire is based on the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) developed by the National Cancer Institute. It assesses eleven common side effects of cancer care and is available for completion from home via the EHR patient portal or in clinic via tablet PC. Implementation was stepwise, beginning with a disease-specific patient population in the main academic cancer center and expanding over two years to include all cancer types, three specialties (radiation oncology, hematology/oncology, gynecologic oncology), and multiple satellite practice locations. Results: PRO collection was initiated for patients with gastrointestinal malignancies in two clinic locations at the main cancer center in 12/2017. During the first 3 months of implementation (12/2017-2/2018), questionnaires were completed for 1838 (56.3%) of 3267 eligible patient visits. Work with practice managers and staff to refine operational workflows led to improvement to a 75.6% capture rate for the period 3/2018 – 5/2018. From 6/2018 through 6/2019, the program was expanded to all multidisciplinary clinics in the main cancer center, as well as eight satellite practices. Aggregate capture rates from 7/2018 through 12/2019 have shown sustained performance, with 101,082 (76.7%) of 131,720 eligible visits captured. Of twelve total clinics participating, eleven have sustained capture rates above 70%, and nine capture over 80% of eligible visits. Questionnaires were completed through the online patient portal 12.1% of the time, with the remainder completed in clinic via tablet PC. Conclusions: Routine PRO collection as standard-of-care is possible across a variety of practice environments in a large, complex health system, with sustained capture of approximately three-fourths of eligible visits. Most patients prefer to complete the questionnaire in clinic.
Effectiveness of adjuvant FOLFOX versus 5FU for colon cancer treatment in community oncology practice using a hybrid study approach.
Authors: Lund Jennifer Leigh , Webster-Clark Michael , Keil Alexander P , Westreich Daniel , Sturmer Til , Sanoff Hanna Kelly 
Published: May 2020

7067 Background: Treatment effects may differ between trials and community settings, in part due to underrepresentation of certain patient subgroups in trials. We used a hybrid approach combining clinical trial and real-world data to compare the effectiveness of adjuvant FOLFOX vs 5FU for stage II-III colon cancer in community oncology practice. Methods: We used Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer (MOSAIC) combined with patients who met trial eligibility criteria within US Oncology from 1/1/2008-5/31/2019. In the combined data, we used logistic regression to estimate the probability of trial enrollment as a function of age, sex, substage, body mass index (BMI), and performance status. We estimated inverse odds of sampling weights and weighted MOSAIC participants to reflect three US Oncology populations: 1) patients meeting trial eligibility, 2) stage III patients, and 3) stage III patients initiating FOLFOX. Within the weighted trial populations, we estimated mortality hazard ratios (HRs) and bootstrapped 95% confidence intervals (CIs) comparing FOLFOX with 5FU. Results: There were 2246 MOSAIC participants and 9335 US Oncology patients. MOSAIC participants were younger, had more stage II cancer, lower BMI, and worse performance status compared with US Oncology patients. After weighting MOSAIC participants to reflect the US Oncology populations, the HRs were attenuated (Table) compared with the original MOSAIC estimate (HR = 0.84; 0.71,1.00). Conclusions: When differences between trial and clinical populations exist and response to therapy varies across subgroups, treatment efficacy can differ from clinical effectiveness. Compared with trial results, we found that effectiveness of FOLFOX versus 5FU was attenuated in community oncology practice. [Table: see text]
Differences in real-world (RW) non-small cell lung cancer (NSCLC) treatment patterns among people living with HIV/AIDS (PLWHA) compared to those without HIV/AIDS (PWoHA).
Authors: Klink Andrew J. , Falkenstein Angelica , Gajra Ajeet 
Published: May 2020

7070 Background: NSCLC is the most common non-AIDS-defining cancer in PLWHA with an estimated prevalence 2-5 times that of PWoHA. Guidelines now support treatment of NSCLC among PLWHA to follow those for PWoHA. However, PLWHA have been often excluded from cancer clinical trials that test novel agents including immunotherapy (IO). This study aimed to assess differences in systemic therapy patterns for advanced NSCLC among PLWHA and PWoHA in the RW. Methods: Adult patients with ≥2 claims for NSCLC between 1/1/13-12/31/18 (earliest claim = index date), ≥3 months data pre/post index date, and no evidence of clinical trial participation, pregnancy or other malignancy prior to index date were identified from Symphony Health longitudinal prescription and medical claims. Patient characteristics and treatment patterns were summarized by descriptive statistics and comparisons by HIV status made on univariate analyses. Times to discontinuation were estimated by Kaplan-Meier method and compared by log-rank tests. Results: There were 60,278 NSCLC PWoHA who received systemic therapy. Of 1,344 PLWHA with NSCLC, 239 (18%) received systemic therapy. PLWHA differed significantly from PWoHA: median age at diagnosis (58 v 68 years), male preponderance (66% v 47%), payer mix (Medicare 26% v 42%; Medicaid 21% v 7%), Charlson Comorbidity Score (median 6 v 1), depression (13% v 5%) and liver disease (8% v 2%), respectively (all P< 0.01). Differences in common systemic therapies among PLWHA v PWoHA include use of first line (1L) carboplatin + paclitaxel (28% v 19%; P< 0.01), 1L erlotinib (6% v 11%, P= 0.02) and 2L gemcitabine (10% v 4%, P< 0.01). IOs were used in 1L among 43 (18%) and 7,149 (12%) of PLWHA v PWoHA, respectively ( P< 0.01). RW surrogates for PFS: median duration of 1L therapy was shorter among PLWHA (1.8 v 2.3 months, P< 0.01); median times from 1L initiation to 2L were similar (5.4 v 4.9 months; P= 0.48). Similar proportion of patients continued onto 2L (32% and 30%) and 3L (10% and 9%) among PLWHA and PWoHA, respectively (all P> 0.05). Total time from diagnosis to last follow-up (RW surrogate for overall survival) was 12.8 v 15.5 months in PLWHA and PWoHA ( P= 0 .07). Conclusions: PLWHA are younger at diagnosis of NSCLC and have higher comorbidity. Important differences in regimen selection and IO utilization exist across PLWHA and PWoHA. PLWHA have shorter 1L than PWoHA. Given higher risk and younger age at diagnosis, additional research is needed to establish screening and treatment guidelines for NSCLC in PLWHA.
Hospitalization for complications due to systemic therapy in the United States.
Authors: Rubens Muni , Ramamoorthy Venkataraghavan , Saxena Anshul , Veledar Emir , McGranaghan Peter , Boulanger Belinda , Chuong Michael David , Hall Matthew David , Kotecha Rupesh , Mehta Minesh P. 
Published: May 2020

7078 Background: Management of complications of systemic therapy for cancer involves significant healthcare burden for both patients and healthcare system. Aim of this study is to estimate trends as well as burden associated with these hospitalizations, using a nationally representative data. Methods: National Inpatient Sample data during 2005-2016 was used to identify complications of systemic therapy using ICD-9 and ICD-10 external cause of injury codes. Primary outcome was hospitalization rate while secondary outcomes were cost and in-hospital mortality related to these complications. Results: There were 443,222,223 hospitalizations recorded during the study period, of which 2,419,722 were due to complications of systemic therapy. The average annual percentage change of these hospitalizations was 8.1%, compared to -0.5% for general hospitalizations. The 3 most common causes for hospitalization were anemia (12.8%), neutropenia (10.8%), and sepsis (7.8%). During the study period, hospitalization rates had highest relative increases for sepsis (1.9 fold) and acute kidney injury (1.6 fold) and highest relative decrease for dehydration (0.21 fold) and fever of unknown origin (0.35 fold). Complications responsible for highest costs per hospitalization were sepsis ($16,834), acute kidney injury ($13,172), and pneumonia ($13,040). Leading causes of in-hospital mortality associated with systemic therapy were sepsis (15.8%), pneumonia (7.6%), and acute kidney injury (7.0%). Conclusions: During 2005-2016, hospitalization rates for systemic therapy complications increased by an annual rate of 8.1%, with anemia, neutropenia, and sepsis as the most common complications requiring hospitalization. Initiatives such as rule OP-35 by the Centers for Medicare and Medicaid Service, improving access and providing coordinated care, early identification and management of symptoms, and expanding urgent care access could decrease these hospitalizations and the burden on healthcare. [Table: see text]
A cost analysis of managing cancer-related pain among hospitalized US cancer patients.
Authors: Alese Olatunji B. , Zhang Chao , Zakka Katerina Mary , Kim Sungjin , Wu Christina , Shaib Walid , Akce Mehmet , Chen Zhengjia , Switchenko Jeffrey M. , El-Rayes Bassel F. 
Published: May 2020

7079 Background: Pain is a common symptom of cancer, affecting patients' function and quality of life. It is also a common cause of hospitalization for cancer patients. The aim of this study was to evaluate the cost of in-hospital pain management among US cancer patients. Methods: A retrospective analysis of data from all US hospitals that contributed to the National Inpatient Sample for 2011-2015 was conducted. All cancer patients admitted for pain management were included in the analysis. Main outcomes were factors significantly associated with hospital length of stay, total charge per hospital stay, and in-hospital mortality. Weighted chi-square test was used for categorical covariates and univariate analysis was performed using a logistic model. Results: 122,776 patient discharges were identified. Mean age was 59.3 years and 52.3% were female. 65.9% stayed in the hospital for longer than 72 hours, with a median total hospital charge of $48,156. Conversely, the median total hospital charge for those spending less than 72 hours on admission was $15,966. Median total charge per hospital stay was similar among insured and uninsured/self-pay patients ($32,879 vs. $32,323; p=0.013), but higher in patients without metastatic disease ($33,315 vs. $29,369; p<0.001). It was also higher in those with the highest income quartile when compared with lowest income patients ($38,223 vs. $30,047; p<0.001). Co-morbid medical illnesses were more prevalent in those with longer hospital stay (15 vs. 12; p<0.001) and the overall in-hospital mortality rate was 8.2%. There was no significant difference in median total hospital charges between those who died in, or those discharged from the hospital ($33,746 vs. $32,795; p<0.001). On multivariate analyses, gender, race, insurance status, diagnosis of metastatic cancer, age, number of co-morbid medical illnesses, year of diagnosis, and median income were significant predictors of length of stay. Race, insurance payor, metastatic cancer, age, and number of co-morbid medical illnesses were significant predictors of total hospital charges, after adjusting for other covariates. Conclusions: In-patient pain management of cancer patients is associated with significant health care costs. Optimization of outpatient pain management strategies could significantly lower the cost of care for cancer.
Interim analysis (IA) of OPTIC: A dose-ranging study of three ponatinib (PON) starting doses.
Authors: Cortes Jorge E. , Lomaia Elza , Turkina Anna , Moiraghi Beatriz , Undurraga Sutton Maria , Pavlovsky Carolina , Rojas Christine , Chuah Charles , Arthur Christopher Kevin , Apperley Jane , Kim Dong-Wook , Hochhaus Andreas , Rousselot Philippe H. , Rosti Gianantonio , Mauro Michael J. , Lipton Jeffrey Howard , Naranjo Daniel , Liu Guohui , Srivastava Shouryadeep , Deininger Michael W.N. 
Published: May 2020

7502 Background: In PACE (NCT01207440) heavily pretreated patients (pts) with chronic-phase CML (CP-CML) had deep, lasting responses to PON; long-term follow-up showed increasing rates of arterial occlusive events (AOEs). We present IA results from OPTIC (NCT02467270), evaluating the association between PON exposure, efficacy, and safety, and response-based dose reduction in pts with CP-CML. Methods: This ongoing, multicenter, randomized phase 2 trial enrolled pts with CP-CML resistant or intolerant to ≥2 TKIs or with a T315I mutation to receive PON at a starting dose of 45 mg (cohort A), 30 mg (B), and 15 mg (C) qd. Doses were reduced to 15 mg qd on achievement of ≤1% BCR-ABL1IS in A/B. Primary endpoint: 12 mo ≤1% BCR-ABL1IS; secondary endpoints include cytogenetic and molecular response and AOE, VTE, and TEAE rates. Results are descriptive at this IA and will be inferential by adjusting multiplicity across 3 cohorts at final analysis. Results: 283 pts were randomized (A/B/C: n = 94/95/94); median age 48 y (18‒81 y). 26% had hypertension history; 2/43/55% received 1/2/≥3 TKIs; 40% had ≥1 baseline (BL) mutations, with 23% T315I. At IA data cutoff (20 Jul 2019), 162 pts (57%; n = 57/51/54) remained on study treatment. Among 282 pts in the safety population, median duration of exposure was ≈1 y (A/B/C, 12.9/11.2/11.0 mo). At 12 mo, 39% (95% CI, 27.6, 50.6), 27% (17.6, 39.1), and 26% (16.5, 38.6) in A, B, and C, respectively, achieved ≤1% BCR-ABL1IS. Additional efficacy in Table. Dose reductions due to efficacy (A/B): 35/21%. Most common TEAEs (any grade/≥3): thrombocytopenia 39/27%, neutropenia 25/17%. AOEs/serious AOEs were reported by (A, B, C) 5%/2%, 4%/3%, and 1%/0%. Dose reductions due to TEAEs: (A/B/C): 44/31/28%; discontinuations due to TEAEs: 18/15/14%. There were 4 (1.4%) on-study deaths; A, sudden death, n = 2; C, pneumonia, n = 2; no deaths were due to AOEs. Clinical trial information: NCT01207440 . Conclusions: OPTIC IA shows a trend toward dose-dependent efficacy and safety and may provide a refined understanding of the PON benefit:risk profile and its relation to dose. Data from longer follow-up may support an alternate dosing regimen for pts with CP-CML. [Table: see text]
Updated results from phase I dose-escalation study of AMG 330, a bispecific T-cell engager molecule, in patients with relapsed/refractory acute myeloid leukemia (R/R AML).
Authors: Ravandi Farhad , Walter Roland B. , Subklewe Marion , Buecklein Veit , Jongen-Lavrencic Mojca , Paschka Peter , Ossenkoppele Gert J. , Kantarjian Hagop M. , Hindoyan Antreas , Agarwal Suresh K , Dai Tian , Khaldoyanidi Sophia , Stein Anthony Selwyn 
Published: May 2020

7508 Background: In this open label phase 1 dose escalation study, safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of AMG 330 were evaluated in patients (pts) with R/R AML (NCT#02520427). Methods: AMG 330 was evaluated as a continuous IV (cIV) infusion using a 3+3 design. Response was assessed per revised IWG criteria. Each cycle (2–4 weeks duration) was followed by an infusion-free interval. Eligible pts were ≥18 y/o with > 5% blasts in bone marrow and ≥1 line/s of prior therapy. Results: As of December 10, 2019, 55 pts (median age, 58.0 [18.0–80.0] years) were enrolled in 16 cohorts. AMG 330 was administered on 4 schedules (0–3 dose steps) prior to the target dose (TD, 0.5–720 µg/day). Dose steps were implemented in the dose schedule design based on the adverse event (AE) profile. Across all schedules, 55 (100%) pts reported treatment-emergent AEs (any grade). AMG 330–related AEs reported in 49/55 (89%) pts included cytokine release syndrome (CRS; 67%; ≥ grade 3 in 13%), (60%) and nausea (20%) as the most frequent AEs. CRS was reversible and occurred in a dose/schedule-dependent manner mostly within the first 24 hours of administration of triggering AMG 330 dose. The frequency and severity of CRS correlated with the dose level and leukemic burden at baseline. AMG 330 exhibited dose-dependent increase in steady state exposures over the studied dose range with clinical PK profile consistent with cIV administration. Eight of 42 evaluable pts responded: 3 complete remissions (CR; including 1 CR with negative measurable residual disease reported after data snapshot), 4 CR with incomplete hematologic recovery, and 1 morphologic leukemia free state. Seven responders who achieved CR/CRi received a TD equal or above the minimal efficacious dose of 120 μg/day. Among analyzed CR/CRi responders, 4/6 (67%) had adverse cytogenetic risk profile, 3/6 (50%) had ≥4 lines of prior therapy and all had relapsed disease. Responders had higher AMG 330 exposures and 3 responders treated with ≥600 μg/day TD remain in CR/CRi: 1 patient for > 5 months after cycle 1, 1 patient bridged to hematopoietic stem cell transplant after cycle 4 and 1 patient is in cycle 3. Preliminary response assessment showed a correlation with lower tumor burden at baseline with a trend towards higher CD8+ lymphocyte count and E:T ratio. Conclusions: AMG 330 dosed up to 720 μg/day provided early evidence of acceptable safety profile, drug tolerability and anti-leukemic activity, and supports further dose escalation. Clinical trial information: NCT02520427 .
Five-year final results of a phase III study of CPX-351 versus 7+3 in older adults with newly diagnosed high-risk/secondary AML.
Authors: Lancet Jeffrey E. , Uy Geoffrey L. , Newell Laura F. , Lin Tara L. , Ritchie Ellen K. , Stuart Robert K. , Strickland Stephen Anthony , Hogge Donna , Solomon Scott R. , Bixby Dale , Kolitz Jonathan E. , Schiller Gary J. , Wieduwilt Matthew Joseph , Ryan Daniel H. , Faderl Stefan , Chang Yu-Lin , Cortes Jorge 
Published: May 2020

7510 Background: CPX-351 (Vyxeos; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of cytarabine [C] and daunorubicin [D], is approved by the FDA and EMA for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Primary analysis of the pivotal phase 3 study (NCT01696084) that formed the basis for these approvals evaluated patients (pts) aged 60-75 y with newly diagnosed high-risk/secondary AML and found that CPX-351 significantly improved median overall survival (OS) vs conventional 7+3, with a comparable safety profile. Here, we report the prospectively planned final 5-y follow-up results from this phase 3 study. Methods: Pts were randomized 1:1 to receive ≤2 induction cycles of CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] as a 90-min infusion on Days 1, 3, 5 [2nd induction: Days 1, 3]) or 7+3 (C 100 mg/m2/d continuously for 7 d + D 60 mg/m2 on Days 1-3 [2nd induction: 5+2]). Pts achieving complete remission (CR) or CR with incomplete platelet or neutrophil recovery could receive up to 2 consolidation cycles. Pts could receive a hematopoietic cell transplant (HCT) at the physician’s discretion. Pts were followed until death or up to 5 y following randomization. Results: In total, 309 pts were randomized to CPX-351 (n = 153) or 7+3 (n = 156). The survival rate at 5 y was higher for CPX-351 vs 7+3 (18% vs 8%; Table). Among pts who died, the most common primary cause of death was progressive leukemia in both arms (CPX-351: 56%; 7+3: 53%). After a median follow-up of 60.65 mo, improved median OS with CPX-351 vs 7+3 was maintained: 9.33 vs 5.95 mo; Kaplan-Meier (KM) OS curves plateaued at ~30 mo. HCT was received by 53 (35%) vs 39 (25%) pts after CPX-351 vs 7+3; among these pts, the survival rate at 5 y was higher for CPX-351 vs 7+3 (52% vs 23%), and median OS landmarked from the HCT date was not reached for CPX-351 vs 10.25 mo for 7+3 (Table). Conclusions: After 5 y of follow-up, improved OS was maintained in this phase 3 study, supporting that CPX-351 has the ability to produce or contribute to long-term remission and survival in older pts with newly diagnosed high-risk/secondary AML. Clinical trial information: NCT01696084 . [Table: see text]