10 research outputs found
Allele survey of <i>NB-LRR3</i> marker and seedling IT with <i>Pgt</i> race 98-1-2,(3),(5),6 on selected ‘Thatcher’ derivatives and historic North American germplasm.
No full textAllele survey of NB-LRR3 marker and seedling IT with Pgt race 98-1-2,(3),(5),6 on selected ‘Thatcher’ derivatives and historic North American germplasm.</p
Additional file 1: of Penile cancer treatment costs in England
No full textInputs Applied in the Markov Model. (DOC 299 kb
Pembrolizumab versus the standard of care for relapsed and refractory classical Hodgkin’s lymphoma progressing after brentuximab vedotin: an indirect treatment comparison
No full textBackground: There is significant unmet need among patients with relapsed and refractory classical Hodgkin’s lymphoma (RRcHL) who have failed multiple lines of therapy, including brentuximab vedotin (BV). Pembrolizumab, an immune checkpoint inhibitor, is one possible treatment solution for this population. Research methods: The objective of this study was to compare progression-free survival (PFS) with standard of care (SOC) versus pembrolizumab in previously BV treated RRcHL patients. A systematic literature review identified one observational study of SOC that was suitable for comparison with KEYNOTE-087, the principal trial of pembrolizumab in this population. Both naïve and population-adjusted (using outcomes regression) pairwise indirect comparisons were conducted. The primary analysis included all patients who had failed BV, with a secondary analysis conducted including only those known to have failed BV that was part of definitive treatment. Results: In the primary analysis, SOC was inferior to pembrolizumab in both the unadjusted comparison (HR 5.00 [95% confidence interval (CI) 3.56–7.01]) and the adjusted comparison (HR 6.35 [95% CI 4.04–9.98]). These HRs increased to 5.16 (95% CI 3.61–7.38) and 6.56 (95% CI 4.01–10.72), respectively, in the secondary analysis. Conclusion: Pembrolizumab offers a significant improvement in PFS compared to SOC in this population.</p
Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, microsatellite instability-high or mismatch repair deficient colorectal cancer - Supplementary Tables
No full textTable S1: Search strategy for Embase Database: Embase 1974 to July 12, 2019Search executed on July 15, 2019Table S2: Search strategy for MEDLINEDatabases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) 1946 to July 12, 2019Search executed on July 15, 2019Table S3: Search strategy for CENTRALDatabase(s): EBM Reviews - Cochrane Central Register of Controlled Trials October 2019 Search executed on July 15, 2019Table S4: Search strategy for Embase - UpdateDatabase: Embase 1974 to April 27, 2020Search executed: April 28, 2020Table S5: Search strategy for MEDLINEDatabases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R) 1946 to April 27, 2020Search executed: April 28, 2020Table S6: Search strategy for CENTRALDatabase(s): EBM Reviews - Cochrane Central Register of Controlled Trials March 2020 Search executed on April 28, 2020Table S7: Eligibility criteria from trials included in systematic reviewTable S8: Patient characteristics from trials included in systematic reviewTable S9: Outcomes from trials included in systematic reviewTable S10: Proportional hazard assumption test (Grambsch and Therneau test) of trials included in the analysisTable S11: Estimated constant hazard ratios of overall survival with pembrolizumab versus competing interventions from fixed-effect and random-effects network meta-analysis; no adjustment for crossover in KEYNOTE-177Table S12: Estimated constant hazard ratios of overall survival with pembrolizumab versus competing interventions from fixed-effect and random-effects network meta-analysis; adjustment for crossover in KEYNOTE-177 using 2-stage modelTable S13: Estimated constant hazard ratios of overall survival with pembrolizumab versus competing interventions from fixed-effect and random-effects network meta-analysis; adjustment for crossover in KEYNOTE-177 using RPSFT modelTable S14: Estimated constant hazard ratios of progression-free survival with pembrolizumab versus competing interventions from fixed-effect and random-effects network meta-analysisTable S15: Estimated time-varying hazard ratios of overall survival with pembrolizumab versus competing interventions from random-effect network meta-analysis; adjustment for crossover in KEYNOTE-177 using RPSFT modelTable S16: Odds ratios estimated from fixed-effect network meta-analysis for treatment-related Grade 3+ adverse events
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Systematic literature review and network meta-analysis of pembrolizumab versus other interventions for previously untreated, unresectable or metastatic, microsatellite instability-high or mismatch repair deficient colorectal cancer - Supplementary Figure
No full textFigure S1: Process for selection of analytical approac
DataSheet_1_Correlation Between Early Time-to-Event Outcomes and Overall Survival in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving Definitive Chemoradiation Therapy: Systematic Review and Meta-Analysis.docx
No full textBackgroundOverall survival (OS) is the most patient-relevant outcome in oncology; however, in early cancers, large sample sizes and extended follow-up durations are needed to detect statistically significant differences in OS between interventions. Use of early time-to-event outcomes as surrogates for OS can help facilitate faster approval of cancer therapies. In locally advanced head and neck squamous cell carcinoma (LA-HNSCC), event-free survival (EFS) was previously evaluated as a surrogate outcome (Michiels 2009) and demonstrated a strong correlation with OS. The current study aimed to further assess the correlation between EFS and OS in LA-HNSCC using an updated systematic literature review (SLR) focusing on patients receiving definitive chemoradiation therapy (CRT).MethodsAn SLR was conducted on May 27, 2021 to identify randomized controlled trials assessing radiotherapy alone or CRT in the target population. Studies assessing CRT and reporting hazard ratios (HRs) or Kaplan-Meier data for OS and EFS were eligible for the analysis. CRT included any systemic treatments administered concurrently or sequentially with radiation therapy. Trial-level EFS/OS correlations were assessed using regression models, and the relationship strength was measured with Pearson correlation coefficient (R). Correlations were assessed across all CRT trials and in trial subsets assessing concurrent CRT, sequential CRT, RT+cisplatin, targeted therapies and intensity-modulated RT. Subgroup analysis was conducted among trials with similar EFS definitions (i.e. EFS including disease progression and/or death as events) and longer length of follow-up (i.e.≥ 5 years).ResultsThe SLR identified 149 trials of which 31 were included in the analysis. A strong correlation between EFS and OS was observed in the overall analysis of all CRT trials (R=0.85, 95% confidence interval: 0.72-0.93). Similar results were obtained in the sensitivity analyses of trials assessing concurrent CRT (R=0.88), sequential CRT (R=0.83), RT+cisplatin (R=0.82), targeted therapies (R=0.83) and intensity-modulated RT (R=0.86), as well as in trials with similar EFS definitions (R=0.87), with longer follow-up (R=0.81).ConclusionEFS was strongly correlated with OS in this trial-level analysis. Future research using individual patient-level data can further investigate if EFS could be considered a suitable early clinical endpoint for evaluation of CRT regimens in LA-HNSCC patients receiving definitive CRT.</p
Integrating efficacy and safety of vedolizumab compared with other advanced therapies to assess net clinical benefit of ulcerative colitis treatments: a network meta-analysis
No full textBecause only one head-to-head randomized trial of biologics for moderate-to-severe UC has been performed, indirect treatment comparisons remain important. This systematic review and network meta-analysis examined efficacy and safety of biologics and tofacitinib for moderate-to-severe UC, using vedolizumab as reference. Relevant studies (N = 19) of vedolizumab, adalimumab, infliximab, golimumab, ustekinumab, and tofacitinib were identified. Study design differences were addressed by assessing efficacy outcomes conditional on response at maintenance initiation. Primary analysis used fixed-effect models to estimate odds ratios for efficacy and safety endpoints. Compared with vedolizumab 300 mg, adalimumab 160/80 mg was associated with less clinical remission (odds ratio, 0.69 [95% credible interval, 0.54–0.88]), and infliximab 5 mg/kg was associated with more clinical remission (1.67 [1.16–2.42]) and response (1.63 [1.15–2.30]). Adalimumab 40 mg, golimumab 50 mg, and ustekinumab 90 mg Q12W had significantly lower clinical remission rates during maintenance (0.62 [0.45–0.86], 0.55 [0.32–0.95], and 0.59 [0.35–0.99]) versus vedolizumab 300 mg Q8W. Response results were similar. Tofacitinib 10 mg had the highest maintenance treatment efficacy estimates and highest infection risk. Network meta-analysis and novel integrated benefit-risk analysis suggest a potentially favorable efficacy-safety balance for vedolizumab vs adalimumab and other advanced UC therapies.</p
sj-docx-1-tam-10.1177_17588359221105024 – Supplemental material for Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50%
No full textSupplemental material, sj-docx-1-tam-10.1177_17588359221105024 for Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50% by Nick Freemantle, Yingxin Xu, Florence R. Wilson, Patricia Guyot, Chieh-I Chen, Sam Keeping, Gerasimos Konidaris, Keith Chan, Andreas Kuznik, Kokuvi Atsou, Emily Glowienka, Jean-Francois Pouliot, Giuseppe Gullo and Petra Rietschel in Therapeutic Advances in Medical Oncology</p
Table_1_Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer.pdf
No full textObjectivesIn randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression.MethodsPatients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring).ResultsIn the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction—the most suitable method based on published guidelines and trial characteristics—produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction.ConclusionsAfter adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.</p
FIGURES 51–53 in Systematics of Paraleucopis Malloch with proposal of Paraleucopidae, a new family of acalyptrate Diptera
No full textFIGURES 51–53. Male terminalia, spermathecae and female tergite 6 of Paraleucopis saguaro sp. nov. 51, male terminalia, lateral view; 52, female tergite 6, dorsal view; 53, spermathecae. Scale bars = 0.1 mm.Published as part of Wheeler, Terry A. & Sinclair, Bradley J., 2019, Systematics of Paraleucopis Malloch with proposal of Paraleucopidae, a new family of acalyptrate Diptera, pp. 301-328 in Zootaxa 4668 (3) on page 323, DOI: 10.11646/zootaxa.4668.3.1, http://zenodo.org/record/344945
