tbuckley/cabot-search huggingface dataset:
Clinical trial metrics: Protocol performance and resource utilization from 14 cancer centers
Authors: H. J. Durivage, K. D. Bridges
Journal: Journal of Clinical Oncology (2009)

6557 Background: Observations at the authors’ institutions and by Dilts et al (JCO 2008, abstr 6534) indicate a high percentage of industry (IND)- and cooperative group (CG)-sponsored therapeutic clinical trials (TCTs) with minimal enrollment. We observed most of the enrollment from a small proportion of the TCTs. To determine if this data was representative of other cancer centers (CCs) we examined accrual to IND- and CG-sponsored adult TCTs from 14 CCs. Methods: Accrual data to IND- and CG-sponsored TCTs was obtained from 14 U.S. CCs. Data for the 3-year period from 2005 through 2007 was analyzed. Pediatric TCTs were excluded. Results: Of 2,685 TCTs, 1455 (54.2%) did not accrue any patients (pts). Only 713 (26.6%) TCTs enrolled &gt; 2 pts and these TCTs provided 88.8% of the total enrollment. Resource utilization: We estimate &gt; 230,000 hours (median: 3,773 hours per CC per year) were devoted to study start up and regulatory maintenance for the 1,455 TCTs that did not accrue any pts (Guidance Document for Implementing Effective Cancer Clinical Trials, www.c-changetogether.org/pubs/default.asp). Conclusions: Approximately 90% of the accrual to IND and CG TCTs is from 26% of these TCTs. Significant resources are used on TCTs that do not contribute significantly to overall accrual. Effective rules governing selection of IND and CG TCTs for activation are needed. Effective rules will enable centers to re-direct valuable resources to useful activities without adverse effect on overall enrollment. [Table: see text] No significant financial relationships to disclose.
Abi Race: A prospective, multicenter study of black (B) and white (W) patients (pts) with metastatic castrate resistant prostate cancer (mCRPC) treated with abiraterone acetate and prednisone (AAP).
Authors: Daniel J. George, Elisabeth I. Heath, A. Oliver Sartor, Guru Sonpavde, William R. Berry, Patrick Healy, Carolyn Winters, Colleen Riggan, Monika Anand, Julie Kephart, Matthew I. Milowsky, Mark T. Fleming, K. C. Balaji, Tian Zhang, Rhonda L. Bitting, Michael Roger Harrison, Megan Ann McNamara, Jennifer A. Freedman, Susan Halabi, Andrew J. Armstrong, Deborah Bruner
Journal: Journal of Clinical Oncology (2018)

LBA5009 Background: Pivotal trials of AAP for patients with mCRPC enrolled few B pts, a population with a higher mortality from prostate cancer. Retrospective data suggests B pts may have higher PSA response rates than W pts treated with AAP for mCRPC. Therefore, we prospectively investigated AAP in B vs. W pts with mCRPC. Methods: Abi Race (NCT01940276) is a prospective, multicenter, parallel group study of AP in 100 men (50 B, 50 W) with mCRPC, self-identified by race. All pts received AA 1000 mg/D and P 10 mg/D (AAP) until disease progression or unacceptable adverse events (AE). The primary objective was radiographic progression-free survival (rPFS); key secondary endpoints include PSA kinetics and safety. Exploratory analyses include SNP, metabolomics and hormonal differences by race. Results: Baseline characteristics among pts were similar. The median rPFS for B and W pts was 16.8 months (mo) in each. However, PSA PFS varied by race; median PSA PFS for B and W pts were 16.6 and 11.5 mo [Table]. B pts also had numerically higher rates of ≥30%, ≥50% and ≥90% PSA decline [Table]. AEs were similar in frequency and severity by race including hypertension (42 vs 40%); however, fatigue was higher in W pts (40 vs 26%), and hypokalemia was higher in B pts (36 vs 18%). SNP profiling revealed differences in key genes involved in androgen metabolism and transport. Conclusions: This is the first prospective multicenter study by race of secondary hormonal therapy in mCRPC. B pts may have greater and more durable PSA response to AAP than W pts. SNP patterns vary by race and will be evaluated for prognostic significance. Further prospective studies in B pts are possible and needed to understand the impact of racial determinants on outcome of new hormonal regimens. Clinical trial information: NCT01940276. [Table: see text]
Safety and tolerability of adjuvant enzalutamide for the treatment of early stage androgen receptor positive (AR+) triple negative breast cancer.
Authors: Tomas Lyons, Ayca Gucalp, Artavazd Arumov, Sujata Patil, Marcia Edelweiss, Mila Gorsky, Tiffany A. Troso-Sandoval, Jacqueline Bromberg, Rachel Ann Sanford, Neil M. Iyengar, Shanu Modi, Ranju Gupta, Tiffany A. Traina
Journal: Journal of Clinical Oncology (2018)

531 Background: A subset of triple negative breast cancer (TNBC) is characterized by androgen receptor (AR) expression and dependence on AR signaling (Doane Oncogene 2006; Gucalp CCR 2013). Enzalutamide (ENZA), an AR-antagonist, has a clinical benefit rate of 33% in evaluable patients(pts) with metastatic AR+ TNBC (Traina et al, JCO 2018). This study tests the feasibility of 1 year (y) of adjuvant ENZA for the treatment (tx) of early stage, AR+ TNBC (NCT02750358). We now report safety data observed in our phase II trial. Methods: Eligible pts have centrally confirmed, Stage I-III, ER/PR < 1%, HER2(-) AR ≥1% BC and completed all planned tx (surgery, (neo)adjuvant chemotherapy and radiation) within 6 months of study start. Tx consists of ENZA 160mg orally daily for 1y with option for 2y at pt discretion. Toxicity assessment per NCI CTCAEv4 every 4 weeks for 12 weeks, then every 3 months. Primary endpoint: feasibility of 1y ENZA, measured as the tx discontinuation rate due to toxicity, withdrawal of consent or tolerability. 46 evaluable pts are required to discriminate between feasibility of 50% and 70%, with type I error 5% and 88% power. Secondary endpoints: feasibility rate at 1y in adherent pts, safety of extended duration ENZA and 3y DFS and OS. Exploratory endpoints: pt reported outcomes and biomarker development. Results: Between 5/2016-1/2018, 38 pts on tx, with complete accrual planned by 6/2018. Pt characteristics: median age 53y(32-80), Stage I/II 81%, III 19%, Grade 2 21%, Grade 3 79%. 35(92%) received chemo: Neo 49%, Adj 51%; Anthracycline/Taxane-based 29 (83%), Platinum 2 (6%), Other 6 (17%). 5(14%) received adjuvant capecitabine for lack of pCR. 79% received XRT. AR > 10% in 24 pts(63.2%) and AR ≤10% in 14(36.8%). Any grade (gr) AE possibly attributed to ENZA: fatigue (31.5%), hot flashes (21%), reduced white blood cells (7.9%), nausea (5.3%) and increased alkaline phosphatase (5.3%). The only ENZA-related gr ≥3 AE was fatigue (1pt, 3%). No seizures were observed. 3 pts had dose reduction due to AE. Conclusions: ENZA administered in the adjuvant setting is well tolerated following definitive locoregional tx and standard of care chemotherapy. No new safety signals were observed. Clinical trial information: NCT02750358.
Residual risk assessment with the Breast Cancer Index (BCI) for prediction of late distant recurrence (DR) in patients from the TransATAC study.
Authors: Ivana Sestak, Yi Zhang, Dennis Sgroi, Catherine A. Schnabel, Jack M. Cuzick, Mitchell Dowsett
Journal: Journal of Clinical Oncology (2018)

529 Background: The Breast Cancer Index (BCI) is a gene-expression based signature comprised of two complementary functional domains: the molecular grade index (MGI) for tumor proliferation, and the HoxB13/IL17BR ratio (H/I) for estrogen signalling. BCI provides a quantitative assessment of the likelihood of overall (0-10yr), late (5-10yr) DR and reported to show endocrine benefit in patients with estrogen receptor positive (ER+) breast cancer. The aim of the current study was to further characterize BCI performance to predict late DR for postmenopausal women with N- and N+ disease treated with either anastrozole or tamoxifen. Methods: 883 women with ER+, N- or N+ (1 to 3 nodes) breast cancer from TransATAC study who were recurrence free at 5 years were included in this analysis. Time to late DR (5 years after diagnosis) was the primary endpoint. Cox regression models were utilized to determine the prognostic value of the BCI and KM-estimates were used to determine 5-10 year DR. Results: 75 late DRs were recorded in all 883 patients who were recurrence free at 5 years. Patients with a high BCI score were associated with a significantly worse outcome compared to those with a low BCI score (HR = 1.88 (1.49-2.39)). This relationship was observed for both N- (HR = 1.96 (1.41-2.72)) and N+ (HR = 1.51 (1.08-2.12)) patients. BCI added significant prognostic information beyond that from CTS in all patients (∆LR-χ2= 11.51, P = 0.0007). For women with N- disease, significant differential risk stratification was observed between low and intermediate groups and between low and high groups. For N+ patients a significant difference was observed between low and high risk groups (HR = 3.10 (1.28-7.49)), but not low and intermediate or intermediate and high. For N+ patients, a BCI model integrating tumor size and grade provided significantly more prognostic value than BCI alone (LR-χ2= 21.34 vs. LR-χ2= 5.86, respectively). Conclusions: In this post-hoc analysis with an expanded group of patients from the TransATAC cohort, BCI was a significant prognostic factor for late DR in both N- and N+ patients, with a combined BCI model providing more prognostic value in N+ patients.
<scp>ABT</scp>‐122, a Bispecific Dual Variable Domain Immunoglobulin Targeting Tumor Necrosis Factor and Interleukin‐17A, in Patients With Rheumatoid Arthritis With an Inadequate Response to Methotrexate
Authors: Mark C. Genovese, Michael E. Weinblatt, Jacob A. Aelion, Heikki T. Mansikka, Paul M. Peloso, Kun Chen, Yihan Li, Ahmed A. Othman, Amit Khatri, Nasser S. Khan, Robert J. Padley
Journal: Arthritis & Rheumatology (2018)

Tumor necrosis factor (TNF) and interleukin-17A (IL-17A) may independently contribute to the pathophysiology of rheumatoid arthritis (RA). This study sought to evaluate the safety and efficacy of ABT-122, a novel dual variable domain immunoglobulin targeting human TNF and IL-17A, in patients with RA who have experienced an inadequate response to methotrexate.Patients with active RA who were receiving treatment with methotrexate and had no prior exposure to biologic agents (n = 222) were enrolled in a 12-week phase II randomized, double-blind, active-controlled, parallel-group study. Patients were randomized to receive either ABT-122 at dosages of 60 mg every other week, 120 mg every other week, or 120 mg every week or adalimumab at 40 mg every other week, administered subcutaneously. The primary efficacy end point was the proportion of patients achieving a ≥20% improvement response based on the American College of Rheumatology criteria for 20% improvement (ACR20) at week 12.Treatment-emergent adverse events were similar across all treatment groups, with no serious infections or systemic hypersensitivity reactions reported with ABT-122. ACR20 response rates at week 12 were 62%, 75%, and 80% with ABT-122 60 mg every other week, 120 mg every other week, and 120 mg every week, respectively, compared with an ACR20 response rate of 68% with 40 mg adalimumab every other week. The corresponding response rates for ACR50 and ACR70 improvement in the ABT-122 dose groups and adalimumab group were 35%, 46%, 47%, and 48%, respectively, and 22%, 18%, 36%, and 21%, respectively.Over the 12-week study period, dual inhibition of TNF and IL-17A with ABT-122 produced a safety profile consistent with that of adalimumb used for inhibition of TNF alone. The efficacy of ABT-122 over 12 weeks at dosages of 120 mg every other week or 120 mg every week was not meaningfully differentiated from that of adalimumab at a dosage of 40 mg every other week in patients with RA receiving concomitant methotrexate.
Everolimus exposure and early metabolic response as predictors for treatment outcomes in breast cancer patients treated with everolimus and exemestane.
Authors: Annelieke Willemsen, Lioe-Fee de Geus-Oei, Maaike De Boer, Jolien Tol, Yvonne Kamm, Paul C. De Jong, Allert Henrik Vos, Jan Willem de Groot, Sasja F. Mulder, Erik H.J.G. Aarntzen, Winald R. Gerritsen, Carla M.L.- Van Herpen, Nielka P. Van Erp
Journal: Journal of Clinical Oncology (2018)

1062 Background: Treating breast cancer patients (BC pts) with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses. We investigated whether everolimus exposure, elderly age, and early metabolic response are predictive of toxicity and effectiveness in these pts. Methods: We collected blood samples from BC pts, 14 and 35 days after starting everolimus and exemestane, to measure everolimus trough level (Cmin). Toxicity, defined as dose interventions (reduction or discontinuation) < 3 months, and progression free survival (PFS) according to RECIST 1.1 were recorded. 18F-FDG-PET was performed at baseline, and 14 and 35 days after start of therapy. SUV normalized by lean body mass was calculated for the maximum voxel and highest peak (SULmax and SULpeak), for up to 5 target lesions. Results: In 44 evaluable pts, the geometric mean (GM) Cmin was higher in pts with dose interventions < 3 months compared to pts without: 17.4 vs 12.3 µg/L (p = .02). The optimal cut-off value to predict toxicity was Cmin > 19.2 µg/L (AUC 0.71, sensitivity 0.55, specificity 0.92). Elderly pts ( > 70 years) compared to pts < 70 years had a shorter median time to dose intervention: 42 vs 141 days (p = .001), but no significant difference in everolimus GM Cmin: 17.6 vs 13.5 µg/L (p = .12). GM Cmin of pts with and without progressive disease (PD) < 3 months was not significantly different: 12.0 µg/L vs 15.2 µg/L, respectively (p = .12). FDG-PET scans of 30 pts were analyzed. The percentage decrease in SULpeak of the lesion with highest avidity at day 14 (SULpeak high d14) was the best predictor of PD < 3 months. Pts with > 11% vs < 11% decrease in SULpeak high at d14 had a median PFS of 411 days vs 90 days respectively (p = .001), and 11 vs 70% of these pts had PD < 3 months. Conclusions: Our results show that everolimus toxicity is related to everolimus Cmin and by monitoring everolimus Cmin, toxicity might be prevented. We recommend diligent monitoring of elderly pts, as they have toxicity more frequently. No relation was observed between everolimus exposure and effectiveness. FDG-PET is able to early identify pts at high risk of early progression. Further validation of these results is required. Clinical trial information: NCT01948960.
Nomograms based on preoperative multiparametric magnetic resonance imaging for prediction of molecular subgrouping in medulloblastoma: results from a radiogenomics study of 111 patients
Authors: Archya Dasgupta, Tejpal Gupta, Sona Pungavkar, Neelam Shirsat, Sridhar Epari, Girish Chinnaswamy, Abhishek Mahajan, Amit Janu, Aliasgar Moiyadi, Sadhana Kannan, Rahul Krishnatry, Goda Jayant Sastri, Rakesh Jalali
Journal: Neuro-Oncology (2018)

Novel biological insights have led to consensus classification of medulloblastoma into 4 distinct molecular subgroups-wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. We aimed to predict molecular subgrouping in medulloblastoma based on preoperative multiparametric magnetic resonance imaging (MRI) characteristics.A set of 19 MRI features were evaluated in 111 patients with histologic diagnosis of medulloblastoma for prediction of molecular subgrouping. MRI characteristics were correlated with molecular subgroups derived from tissue samples in 111 patients (WNT = 17, SHH = 44, Group 3 = 27, and Group 4 = 23). Multinomial logistic regression of imaging parameters was performed on a training cohort (TC) of 76 patients, representing two-thirds of randomly selected patients from each of 4 molecular subgroups, to generate binary nomograms. Validation of these nomograms was performed on the remaining 35 patients as the validation cohort (VC).Medulloblastoma subgroups could be accurately predicted by preoperative MRI features in 74% of cases. Predictive accuracy was excellent for SHH (95%), acceptably high for Group 4 (78%), modest for Group 3 (56%) and worst for WNT (41%) subgroup medulloblastoma. SHH-specific nomogram was associated with excellent correlation between TC and VC, with area under the curve (AUC) of 0.939 and 0.991, respectively. AUC for Group 4 was acceptable at 0.851 and 0.788 in TC and VC, respectively; however, these values were consistently suboptimal in WNT and Group 3 medulloblastoma.The predictive accuracy of MRI-based nomograms was excellent for SHH and encouraging for Group 4 medulloblastoma. Further work is needed for Group 3 and WNT-pathway medulloblastoma.
Veterans Health Administration Home-Based Programs and Cardiac Rehabilitation—Reply
Authors: David W. Schopfer, Mary A. Whooley
Journal: JAMA Internal Medicine (2018)

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Insulin decreases expression of the proinflammatory receptor proteinase-activated receptor-2 on human airway epithelial cells
Authors: Vivek D. Gandhi, Nami Shrestha Palikhe, Shereen M. Hamza, Jason R.B. Dyck, Jean Buteau, Harissios Vliagoftis
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 18220: Impact of Lipid and Blood Pressure Reduction on Erectile Dysfunction in Persons at Intermediate Risk for Cardiovascular Disease
Authors: Philip Joseph, Eva Lonn, Jackie Bosch, Swaminathan Balakumar, Salim Yusuf
Journal: Circulation (2016)

Introduction: Erectile dysfunction (ED) is associated with cardiovascular disease (CVD) risk factors, and predicts future CVD, suggesting that ED and atherosclerosis share common mechanisms. Howeve...
Impact of number of dissected axillary lymph nodes on survival in breast cancer patients.
Authors: Ahmed M Maklad, Emad Eldin Nabil, Ashraf Elyamany
Journal: Journal of Clinical Oncology (2018)

e12593 Background: For patients with breast cancer, axillary dissection was a standard treatment, especially with patient with positive metastases in the sentinel nodes. For some patients axillary dissection might be over-treatment, including those who have had a mastectomy. Especially with the new trend of many radiation-therapy centers, provide radiation-therapy for any number of positive lymph nodes. The aim of our work is to evaluate the impact of number of dissected axillary lymph nodes (LN), on overall survival (OS) and progression free survival (PFS) in breast cancer patients. Methods: This is a retrospective study done in Sohag University hospitals between periods 1/2008 till 12/2014. One hundred and three patients diagnosed with breast cancer were reviewed regarding number of axillary lymph nodes dissected in correlation to progression free survival, overall survival. We divided the patients into two groups according to number of dissected lymph nodes more than 10 LNs (72 patients or less than ten LN (31 patients)). The patients were categorized into N0 (No LN positive), N1 (1-3 LN positive), N2 (3-9LN positive) in both groups, and N3 in first group only as it is more than 10 LN positive Results: Median PFS for patients having more than 10 LN excised was for N0, N1, N2, N3 5.19, 4.77, 4.14, 3.69 years respectively ,while in the group with less than 10 LN excised PFS was 4.5, 4.14, 4.08 years respectively with no significant difference between both groups P = 0.290. As regard median OS for patients having more than 10 LN excised was for N0, N1, N2, N3 5.57, 5.94, 4.97, 4.61 years respectively while in the other group having less than 10 LN excised OS was 5.4, 5.14,5.14 years respectively with P = 0.117. The incidence of grade 3 and 4 lymphedema was not different between both arms P = 0.913. Conclusions: Axillary lymph nodes management is controversial and needs to be clarified, we tried to evaluate impact of surgical axillary dissection on survival in breast cancer patients. We found no significant OS or PFS differences with higher LN dissection compared with less LN dissection, but this needs further prospective studies.
PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma
Authors: Michael R. Migden, Danny Rischin, Chrysalyne D. Schmults, Alexander Guminski, Axel Hauschild, Karl D. Lewis, Christine H. Chung, Leonel Hernandez-Aya, Annette M. Lim, Anne Lynn S. Chang, Guilherme Rabinowits, Alesha A. Thai, Lara A. Dunn, Brett G.M. Hughes, Nikhil I. Khushalani, Badri Modi, Dirk Schadendorf, Bo Gao, Frank Seebach, Siyu Li, Jingjin Li, Melissa Mathias, Jocelyn Booth, Kosalai Mohan, Elizabeth Stankevich, Hani M. Babiker, Irene Brana, Marta Gil-Martin, Jade Homsi, Melissa L. Johnson, Victor Moreno, Jiaxin Niu, Taofeek K. Owonikoko, Kyriakos P. Papadopoulos, George D. Yancopoulos, Israel Lowy, Matthew G. Fury
Journal: New England Journal of Medicine (2018)

No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose-escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous-cell carcinoma.We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous-cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic-disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review.In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic-disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow-up was 7.9 months in the metastatic-disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic-disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event.Among patients with advanced cutaneous squamous-cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498 .).