tbuckley/cabot-search huggingface dataset:
Abstract 16432: Optimal Dosing of ACE Inhibitors and ARBs in Chronic Heart Failure Patients - A Meta-analysis of Randomized Controlled Trials
Authors: Aaqib H Malik, Yasir Akram, Senada S Malik
Journal: Circulation (2015)

Introduction: Congestive heart failure (CHF) is associated with significant morbidity and mortality. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are proven to be beneficial for improved survival and better quality of life in Heart failure patients. Optimal dosing of these agents presents a challenging question till date and controversy still surrounds whether similar health benefits can be achieved through lower dosages of ACE inhibitors and ARBs. Our aim was to determine whether there is a significant mortality benefit in CHF patients who receive higher dosage of ACE inhibitors and ARBs compared to lower dosage. Methods: Medline Indexed and Non-indexed, Cochrane Central, CINAHL and PsychINFO were searched for randomized controlled trials (RCTs) published till date. All RCTs that compared the clinical impact of high versus low dosage of ACE inhibitors or ARBs in heart failure patients were identified. Two independent investigators assessed the studies against an a priori inclusion criteria and disagreements were resolved by mutual discussion. Results: We used reported event rates for all studies to compute cumulative odds ratio and p-value for mortality. Summary effects were estimated using random effects models in RevMan 5.2. Of 1610 potentially relevant studies, a total of 5 studies (9027 patients) met our inclusion criteria and had data available on mortality events. The pooled estimate of the included studies showed a statistically significant 10% reduction in mortality of CHF patients who received higher dosage of ACE inhibitor and ARBs. (Odds Ratio: 0.90; 95% confidence interval 0.82,0.99). Heterogeneity was tested and it showed no evidence of publication bias. Conclusions: In conclusion, our meta-analysis of RCTs shows that higher dosage of ACE inhibitors and ARBs have a clinically and statistically significant mortality benefit over lower dosage in the management of chronic heart failure patients.
Comparison of Health, Development, Maternal Bonding, and Poverty Among Children Born After Denial of Abortion vs After Pregnancies Subsequent to an Abortion
Authors: Diana Greene Foster, M. Antonia Biggs, Sarah Raifman, Jessica Gipson, Katrina Kimport, Corinne H. Rocca
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> Evidence indicates that there are potential health, development, and maternal bonding consequences for children born from unwanted pregnancies. <h3>Objective</h3> To examine the association of women receiving or being denied a wanted abortion with their children’s health and well-being. <h3>Design, Setting, and Participants</h3> A 5-year longitudinal observational study with a quasi-experimental design conducted between January 18, 2008, and January 25, 2016, examined women who received abortions just under the gestational age limit of 30 abortion facilities across the United States and women who were denied abortion just beyond the gestational age limit in these facilities. Analyses compared the children of 146 women who were denied an abortion (index children) with children born to 182 women who received an abortion and had a subsequent child within 5 years (subsequent children). Interview-to-interview retention averaged 94.5% (6895 of 7293) across the 11 semi-annual interviews. <h3>Exposures</h3> Being born after denial of abortion vs after a new pregnancy subsequent to an abortion. <h3>Main Outcomes and Measures</h3> Perinatal outcomes and child health, child development, maternal bonding, socioeconomics, and household structure. <h3>Results</h3> This study included 328 women who had children during the study period (mean [SD] age at study recruitment, 23.7 [4.9] years). There were no differences by study group in consent to participate in the study, completion of first interview, or continuation in the study. Among the 328 children in the study (146 index children and 182 subsequent children), there were 163 girls and 165 boys. Perinatal and child health outcomes were not different between subsequent and index children, and there was no clear pattern of delayed child development. However, mixed-effects models adjusting for clustered recruitment and multiple observations per child revealed that poor maternal bonding was more common for index children compared with subsequent children (9% vs 3%; adjusted odds ratio, 5.14; 95% CI, 1.48-17.85). Index children lived in households with lower incomes relative to the federal poverty level than did subsequent children (101% vs 132% of federal poverty level; adjusted regression coefficient, –0.31; 95% CI, –0.52 to –0.10), and were more likely to live in households without enough money to pay for basic living expenses (72% vs 55%; adjusted odds ratio, 5.16; 95% CI, 2.34-11.40). <h3>Conclusions and Relevance</h3> These findings suggest that access to abortion enables women to choose to have children at a time when they have more financial and emotional resources to devote to their children.
A pediatric phase I study of larotrectinib, a highly selective inhibitor of the tropomyosin receptor kinase (TRK) family.
Authors: Theodore Willis Laetsch, Steven G. DuBois, Ramamoorthy Nagasubramanian, Brian Turpin, Leo Mascarenhas, Noah Federman, Mark Reynolds, Steven Smith, Scott Cruickshank, Michael Craig Cox, Alberto S. Pappo, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2017)

10510 Background: Larotrectinib is the first selective small-molecule inhibitor of TRKA, B, and C in clinical development. Data from the adult phase I trial demonstrate prolonged responses in patients (pts) with TRK fusions and a favorable tolerability profile. Methods: This multicenter, rolling 6 phase I study enrolled pts with refractory solid or CNS tumors aged ≥ 1 month – 21 years. Pts were dosed orally BID on a continuous 28-day schedule either by capsule or solution. Pharmacokinetic (PK)-directed intra-subject dose escalation was permitted, with exposures targeting the adult recommended Phase II dose (RP2D) of 100 mg BID. The primary objective was to define the MTD / RP2D; secondary objectives included PK and efficacy using RECIST v1.1. Results: As of December 31, 2016, 17 pts (12 with TRK fusions, 5 without TRK fusions) with a median age of 5.2 years (0.4 – 18.3) were enrolled to 3 dose levels. Pts were enrolled with fusions of all 3 NTRK genes: NTRK1 (n=6), NTRK2 (n=1), and NTRK3 (n=5) in heterogeneous tumor diagnoses: infantile fibrosarcoma (IFS) (n=6), other sarcoma (n=4), and papillary thyroid cancer (n=2). Most common AEs regardless of attribution were vomiting, diarrhea, and fatigue. While 8 (47%) pts experienced grade 3-4 AEs, none were attributed to larotrectinib. No DLTs were observed and an MTD was not established. Both formulations delivered dose-dependent PK comparable to the adult RP2D at dose level 3. 12 pts (10 with TRK fusions, 2 without TRK fusions) remain on treatment with median follow-up of 2.8 months (0.7 – 8.4). Among TRK fusion pts, the vast majority have achieved confirmed RECIST responses regardless of tumor diagnoses. No responses were seen in pts without TRK fusions (n=4). 5 pts discontinued therapy, including 2 with TRK fusions: 1 pt with IFS had sufficient response to allow tumor resection, and 1 pt with IFS progressed with a documented acquired resistance mutation. Conclusions: Larotrectinib has demonstrated a favorable tolerability profile and histology-independent efficacy in pediatric pts harboring TRK fusions. Updated safety and efficacy data will be presented, including the RP2D, response rate, duration of response, and use of larotrectinib in the pre-surgical setting. Clinical trial information: NCT02637687.
Longitudinal physical activity assessment in post-surgical gynecologic cancer patients.
Authors: Jessica Gorzelitz-Liebhauser, Erin S. Costanzo, Ryan J. Spencer, Meredith E. Rumble, Stephen L. Rose, Lisa Cadmus-Bertram
Journal: Journal of Clinical Oncology (2017)

e21582 Background: Physical activity is a key determinant of health, and exercise can be effective for decreasing anxiety and depression and improving quality of life in cancer survivors. The primary aim of this study was to report the trajectory of physical activity over time for post-operative gynecologic cancer patients. The secondary aim was to identify correlates of total physical activity over time. Methods: The study population included patients who underwent surgery for endometrial (n = 80) or ovarian (n = 43) cancer and wore an accelerometer for a 3-day period at 1 week, 1 month and 4 months after surgery. Accelerometer data were captured during all waking hours and were transformed into categories of light, moderate and vigorous intensity physical activity. The outcome of interest was total minutes of moderate to vigorous intensity physical activity (MVPA) collected over the three day period at each time point, analyzed using a linear mixed effect model approach, assessing the correlates of age, body mass index (BMI), self-rated health, laparotomy vs. laparoscopic (endometrial only) and neoadjuvant chemotherapy yes/no (ovarian only). Results: Mean age was 58.8 ± 10.1 years with mean BMI of 35.5±10.3 kg/m 2 . Over each three-day period, patients performed 7 ± 12 minutes of total accumulated MVPA at 1 week, 20 ± 41 minutes of total MVPA at 1 month, and 25 ± 36 minutes at 4-months post-surgery (p = 0.01). Federal guidelines recommend approximately 70 minutes of moderate intensity activity over a three-day period to collect 150 minutes of moderate activity a week. Better self-rated health at baseline was associated with increased activity over time (p = 0.02). BMI, age, type of surgery or use of neoadjuvant chemotherapy did not predict physical activity in patients of either disease site. Conclusions: Physical activity increased over time for endometrial and ovarian cancer patients. Self-reported health at baseline was also positively associated with increased moderate-vigorous physical activity over time. There is insufficient evidence to show that BMI significantly contributes to changes in moderate-to-vigorous physical activity over time. Future research should address barriers to activity and novel interventions.
Cancer patient-reported knowledge and preferences for liquid biopsies and blood biomarkers at a comprehensive cancer centre.
Authors: Min Joon Lee, Shirley Xue Jiang, Yizhuo Gao, Katrina Hueniken, Lin Lu, Lawson Eng, Alexandra McCartney, Tamara Obuobi, Nathan Kuehne, Badr Id Said, Mindy Liang, Hadas Sorotsky, M. Catherine Brown, Wei Xu, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

6587 Background: Novel blood-based biomarkers, including cell-free DNA and plasma signatures, are becoming a reality in precision oncology. Yet, little is known about cancer patients’ perspectives on blood biomarkers in clinical practice. Methods: A 54-item self-administered questionnaire and four interviewer-administered trade-off scenarios were administered to cancer patients across all sites at Princess Margaret Cancer Centre. Results: Of 632 eligible patients, 66% (n = 417) completed the survey; 54% female; median age 61 (range 18-101) years. Patients had a median accuracy score of 18% (range 0-81%) on their knowledge of the role of biomarkers on their own cancer. Disease site was significantly associated with knowledge (P = 0.029); patients with breast, genitourinary, and thoracic cancers performed better than patients of other sites. Females (P = 0.012) and those with higher education (P = 0.019) and income (P = 0.0016) also scored better. Scores were not associated with the stage at diagnosis, time since diagnosis, age or ethnicity. Using chart review, 91% had been evaluated in at least one setting with either tissue, blood, or clinical biomarkers; however, only 20% of them were aware of this. In the scenario-based preference testing, if given a choice, 90% (n = 372) preferred a liquid (blood) over a tissue biopsy; however, these patients only accepted a median waiting period of one additional week (IQR: 0-3 weeks) and a 5% decrease (IQR 0-10%) in sensitivity of identifying the right treatment before switching their preference to the tissue biopsy. The majority (n = 216; 58%) were not interested in switching even with no potential complications from tissue biopsy. People with higher education were more likely to switch based on the level of risk (P < 0.001). Conclusions: Although patients had limited understanding of their cancer-specific blood-based biomarkers, 90% preferred blood over tissue biomarkers, but with little tolerance to waiting longer for results or decreased test sensitivity. Developing blood biomarkers and performing liquid biopsies are therefore desirable to patients, but only if they had similar or improved test characteristics over their tissue counterparts.
Epoetin zeta in patients with hematological malignancies with or without iron supplementation: A sub-analysis of the SYNERGY study.
Authors: Isabelle Laure Ray-Coquard, Kamel Laribi, Christian Gisselbrecht, Dominique Spaeth, Emna Kasdaghli, Florian Scotte
Journal: Journal of Clinical Oncology (2016)

e21680 Background: Epoetin zeta (Retacrit, Hospira, a Pfizer company) is an erythropoiesis-stimulating agent that is well tolerated and efficacious in treating patients with chemotherapy-induced anemia (CIA).1 This study evaluated the effect of epoetin zeta, with or without iron, on CIA in patients with hematological malignancies. Methods: In this observational, longitudinal, prospective, multicenter study conducted in France from a representative, random sample of oncologists and hematologists, adults ( ≥ 18 years) being treated for cancer who were eligible for treatment with epoetin zeta were followed for 12–16 weeks. A sub-analysis of patients with hematological malignancies is presented here. Results: In the analysis population, 423 patients had hematological malignancies; 62.4% (n = 264) had lymphoma and 32.2% (n = 136) had multiple myeloma. The majority of patients in both sub-groups had advanced disease, and an Eastern Cooperative Oncology Group performance status of 0–2. Most patients had mild or moderate anemia at inclusion; mean hemoglobin was 9.5 g/dL. Iron supplementation was not commonly given to patients with hematological malignancies; 9.5% received iron supplementation (32.5% (n = 13) intravenously and 67.5% (n = 27) orally). The majority of patients responded to epoetin zeta treatment (74.4% lymphoma, n = 189 and 81.3% multiple myeloma, n = 100). Iron supplementation did not increase the response to epoetin zeta in the lymphoma (p = 0.301) or multiple myeloma (p = 1.000) sub-populations. Patient-scored effect on fatigue was not significantly different between patients receiving iron supplementation and those who did not in the lymphoma (p = 0.503) or multiple myeloma (p = 0.619) groups. Adverse events were reported in 0.8% and 1.5% of patients with lymphoma and multiple myeloma and were primarily thromboembolic events. Conclusions: Epoetin zeta is effective for treating CIA, regardless of hematological malignancy type. Iron supplementation did not affect treatment response in this population. Epoetin zeta was well tolerated in patients with hematological malignancies, with low rates of thromboembolic events. Reference 1. Michallet m et al. BMC Cancer 2014;14:503 Clinical trial information: NCT02158169.
Phase 1b/2 keynote-365 trial: Pembrolizumab (pembro) combination therapy in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Evan Y. Yu, Haiyan Wu, Charles Schloss
Journal: Journal of Clinical Oncology (2017)

TPS5089 Background: Approved treatments for mCRPC (eg, enzalutamide and docetaxel) may increase programmed death ligand 1 (PD-L1) expression and facilitate neoantigen release. In phase 1b and 1/2 trials, pembro, an anti–PD-1 antibody, has produced antitumor responses in previously treated mCRPC as monotherapy and in combination with enzalutamide. Olaparib, a PARP inhibitor, has shown activity in mCRPC with DNA-repair defects. The nonrandomized, multicohort, open-label KEYNOTE-365 study (NCT02861573) will evaluate the safety and efficacy of pembro with olaparib (cohort A), docetaxel + prednisone (cohort B), or enzalutamide (cohort C) in mCRPC. Methods: Cohort allocation depends upon prior treatment: cohort A requires prior docetaxel (treatment with 1 other chemotherapy and ≤2 second-generation hormonal manipulations is allowed); cohort B requires prior abiraterone acetate or enzalutamide (but not both); cohort C requires prior abiraterone acetate. Additional eligibility criteria include confirmed prostate adenocarcinoma, disease progression (PD) ≤6 months before screening, ongoing androgen deprivation (serum testosterone &lt; 50 ng/dL), and provision of nonirradiated tumor sample. Pembro 200 mg will be given every 3 weeks (Q3W) with either olaparib 400 mg twice daily (cohort A), docetaxel 75 mg/m 2 Q3W + prednisone 5 mg twice daily (cohort B), or enzalutamide 160 mg once daily (cohort C). Pembro treatment will continue for up to 35 cycles or until PD or unacceptable adverse events (AEs). Patients in cohort B may receive a maximum of 10 cycles of docetaxel + prednisone. Patients who discontinue 1 of 2 drugs in a combination because of a treatment-related AE may continue to receive the other drug until PD. Response will be evaluated by prostate-specific antigen (PSA) levels Q3W and by imaging Q9W for the first year and Q12W thereafter. Primary end points are safety and PSA response rate (decline of ≥50% from baseline twice ≥3 weeks apart). Secondary end points include time to PSA progression, progression-free survival, overall survival, and overall response rate. Enrollment will continue until 70 patients are enrolled for each cohort. Clinical trial information: NCT02861573.
Racial/ethnic differences in comprehension of biospecimen sharing/banking: University of Rochester Cancer Center NCI Community Oncology Research Program (URCC-NCORP) nationwide study in 710 cancer and healthy subjects.
Authors: Matthew Asare, Charles Stewart Kamen, Gary R. Morrow, Charles E. Heckler, Luke Joseph Peppone, Joan Long, Sharon Cole, Adedayo A. Onitilo, Michelle M Feige, Lori M. Minasian, Dave Windler, Carol J. Weil, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2017)

e18077 Background: Informed consent documents containing language about biospecimen storage/sharing (BSS) may be a barrier to minority participation in cancer research. We explored this issue in a nationwide URCC-NCORP observational study by assessing whether breast cancer patients and healthy control subjects, who provided consent to a cognitive function study, differed in their understanding of the ways their BSS could be used by researchers. Methods: We analyzed cross-sectional data from female breast cancer patients scheduled to receive chemotherapy at NCORPs and healthy controls. After reading a consent form related to BSS and consenting to participate in a study about cognitive function, participants’ understanding of BSS was evaluated using four items for biospecimen sharing (score 0-4); three items for relevance to care (score 0-3); nine items for biospecimen use (score 0-9); and six for research purpose (score 0-6); a higher score indicates better understanding. Linear models were used to compare the mean scores between white and non-white subjects, adjusting for education and baseline reading comprehension (WRAT). Results: 461Breast cancer patients and 249 healthy controls completed the survey. The adjusted linear models showed that white subjects scored higher than non-whites (mean scores 14.43 vs. 13.43) on the survey questions overall (p &lt; 0.05), after accounting for education and WRAT. White subjects were more likely than non-whites to correctly answer all the questions for the biospecimen use (42.1% vs. 34.4%, p &lt; 0.22), biospecimen sharing (31.3% vs. 28.1%, p &lt; 0.74), relevance to care (35.1% vs. 17.2%, p &lt; 0.01), and research purpose (4.1% vs. 1.4%, p &lt; 0.97). Conclusions: Our research suggests that informed consent comprehension related to BSS is low overall across all racial/ethnic backgrounds, but non-white subjects’ scores remained lower than whites even after adjusting for education and WRAT. Efforts should be made by researchers to make it easier for all study subjects, especially non-white subjects, to understand informed consent form and BSS.
A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent/metastatic head and neck cancer.
Authors: Ryan J. Brisson, Allison Dekker, Jonas A. De Souza, Vassiliki Saloura, Everett E. Vokes, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2017)

6039 Background: R/M HNC carries a poor prognosis with a median survival of 10-12 months. PI3K pathway aberrations are present in 30% of HNC. This pilot dose-escalation study assesses the safety and tolerability of the PI3K inhibitor buparlisib when given concurrently with cetuximab in R/M HNC, as well as assess efficacy in an expansion cohort. Methods: Patients (pts) with R/M HNC who were not amenable to curative intent therapy were enrolled. Pts were given oral buparlisib starting day -7 and daily thereafter. The dose of buparlisib was escalated in a 3+3 design (Level 1: 80mg daily, Level 2: 100 mg daily) followed by a dose expansion cohort. The maximum dose of buparlisib was 100 mg daily. Cetuximab (500mg/m 2 ) was given intravenously every 14 days starting day 0. Pts continued on treatment until progression of disease. Prior cetuximab failure was allowed. Results: Of the 12 pts enrolled, 10 had at least 2 previous treatment regimens (11 with prior cetuximab). 5 pts were HPV+, 4 were HPV-, and 3 had unknown HPV status. 3 pts were treated at the 80 mg dose level while 9 were treated at the 100 mg dose level (3 + 6 patient expansion). Treatment was well tolerated with 2 pts experiencing grade 3 adverse events (AEs) (no grade 4 AEs). The most common AEs were fatigue (83.3%), maculopapular rash (50.0%), and anorexia (50.0%). 3 pts experienced grade 1 anxiety. There were no SAEs. Of the 10 pts who were evaluable for response one patient achieved a PR (10%), and 4 achieved stable disease (40%) per RECIST 1.1. Median overall survival was 280 days (HPV+: 370 days, HPV-:191 days). The study was closed early due to poor enrollment on the expansion cohort as patients opted for concurrently open immunotherapy trials. Conclusions: Based on this pilot study, buparlisib plus cetuximab proved to be well-tolerated and showed limited evidence of activity in a heavily pre-treated patient population. Further research is warranted to determine activity of buparlisib in a larger cohort of R/M HNC. Clinical trial information: NCT01816984.