An analysis to quantify the overall survival (OS) benefit of sipuleucel-T accounting for the crossover in the control arm of the IMPACT study.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 144-144
Author(s):  
Chadi Nabhan ◽  
Leonard G. Gomella ◽  
Todd DeVries ◽  
James Boyd Whitmore ◽  
Mark Walter Frohlich ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Failure Time ◽  
Cellular Immunotherapy ◽  
Impact Study ◽  
Treatment Benefit ◽  
Positive Treatment Effect ◽  
Positive Treatment ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Impact

144 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (mCRPC). Our previous analyses on the effect of salvage crossover treatment with a product constructed from previously frozen cells (APC8015F) on OS in the control arms of mCRPC studies of sipuleucel-T suggested a positive treatment effect with salvage therapy (George DJ et al. JCO 2011;29:abstr 139). To quantify how treatment with APC8015F might have impacted the OS of the IMPACT study, we performed an exploratory analysis adjusting for the potential bias that salvage APC8015F might have had in estimating the OS advantage of sipuleucel-T. Methods: After objective disease progression, patients (pts) in the control arm were offered 3 infusions of APC8015F, an autologous immunotherapy made from cells cryopreserved at the time of control generation. A rank-preserving structural failure time (RPSFT) model, as previously described, was applied to adjust the sipuleucel-T treatment effect. Results: In the 512-pt IMPACT study, there was a 4.1-month median improvement in OS (25.8 vs 21.7 months) for sipuleucel-T compared to control (HR=0.78; 95% CI: 0.61, 0.98; p=0.032). 109/171 (64%) of control pts received APC8015F; other post-progression interventions were balanced. Median OS was 23.8 months for control pts receiving APC8015F and 11.6 months for control pts not receiving APC8015F. Using the RPSFT model, and assuming APC8015F was equally as effective as sipuleucel-T, the estimate of median OS for control was 18.0 months (HR=0.60, 95% CI: 0.41, 0.95), representing a 7.8-month median improvement in OS in favor of sipuleucel-T. Results from extensions of the RPFST model, where APC8015F is assumed to have less treatment effect than sipuleucel-T, will be presented. Conclusions: Adjusting for a positive effect of APC8015F in the control arm resulted in a sipuleucel-T OS treatment benefit in the IMPACT study ranging from 4.1 to 7.8 months. These results support a greater treatment effect of sipuleucel-T than reported in the IMPACT study and should be factored into future studies without APC8015F crossover.

Impact of salvage therapy with APC8015F on the overall survival (OS) benefit achieved with sipuleucel-T in three phase III studies of metastatic castrate-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15120-e15120
Author(s):  
Leonard G. Gomella ◽  
Chadi Nabhan ◽  
Todd DeVries ◽  
James Boyd Whitmore ◽  
Mark Walter Frohlich ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Salvage Therapy ◽  
Failure Time ◽  
Phase Iii ◽  
Comparable Efficacy ◽  
Cellular Immunotherapy ◽  
Three Phase ◽  
Castrate Resistant ◽  
The Impact ◽  
Phase Iii Studies

e15120 Background: Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. Three phase III sipuleucel-T trials (D9901, D9902A and D9902B [IMPACT]) allowed control patients (pts) to receive salvage treatment with an autologous product derived from previously frozen cells (APC8015F). We previously reported that salvage therapy with APC8015F demonstrated no deleterious effect and may have improved outcomes in control pts, potentially reducing the observed survival benefit seen with sipuleucel-T. Thus, we performed an exploratory analysis of pooled data from phase III studies to estimate the impact of APC8015F treatment on the OS benefit conferred by sipuleucel-T. Methods: We analyzed the effect of salvage APC8015F therapy on OS, and used a rank-preserving structural failure time (RPSFT) model to estimate control arm OS if treatment with APC8015F had not occurred. This allows estimation of the effect of sipuleucel-T treatment on OS, adjusting for salvage effect. Results: Median OS from randomization in the three pooled trials was 25.4 months with sipuleucel-T (n=488) and 21.5 months with control (n=249). Of the control arm pts, 165 (66.3%) subsequently received APC8015F. Median OS from randomization in the control population was 23.6 months for pts receiving APC8015F and 12.7 months for those who did not. Using the RPSFT model, and assuming APC8015F was as effective as sipuleucel-T, the estimate of median OS for control pts was 17.3 months, representing an 8.1 month median increase in OS with sipuleucel-T. Results from extensions of the RPSFT model, where APC8015F is assumed to have less treatment effect than sipuleucel-T, will be presented. Conclusions: These analyses estimated a median OS benefit for sipuleucel-T between 3.9 and 8.1 months, assuming that APC8015F had either no efficacy or comparable efficacy to sipuleucel-T, respectively. The results suggest a possible greater treatment effect of sipuleucel-T than was reported in the three phase III studies. Future studies should account for potential crossover treatment bias as this may diminish estimates of OS benefit.

scholarly journals (Nano)Technology for Managing Plant Organisms with the Help of Targeted Impact Using the Signals of the Physical Nature

2015 ◽  
Vol 32 ◽  
pp. 32-35
Author(s):  
V.V. Karpachev ◽  
N.L. Voropaeva ◽  
T.G. Belonozhkina ◽  
E.V. Naumov ◽  
M.M. Vasilev ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Agricultural Production ◽  
Growth And Development ◽  
Physical Nature ◽  
Control Technology ◽  
Nano Technology ◽  
Positive Treatment Effect ◽  
Positive Treatment ◽  
Growth Development ◽  
The Impact

One of the major problems of agricultural production has been to improve the sowing qualities of seeds to increase yields of various crops. In this regard, of particular interest is the control technology of vegetable organisms by "address the impact of" signals of the physical nature. Plasma treatment of seeds influences the growth and development of the amaranth. The effectiveness of treatment depends on the exposure time of the exposure. The largest positive treatment effect of the plasma on the growth, development and yield of amaranth has been observed when the exposure 60 seconds, leading to increased yields.

scholarly journals Efficacy of Zoledronic Acid in Patients with Systemic Osteoporosis and Problem of «Non Respondents» to the Treatment

2015 ◽  
Vol 22 (4) ◽  
pp. 39-43
Author(s):  
S. S Rodionova ◽  
Yu. V Buklemishev
Keyword(s):  
Bone Formation ◽  
Treatment Effect ◽  
Biochemical Tests ◽  
Zolendronic Acid ◽  
Bone Formation Markers ◽  
Study Results ◽  
Positive Treatment Effect ◽  
Positive Treatment ◽  
The Relationship ◽  
Mineral Bone Density

Prospective study of zolendronic acid efficacy was performed in 112 patients with systemic osteoporosis. Study results confirmed the presence of patients who did not response to the treatment: in 15.7 % of observations reduction of mineral bone density (BMD) continued to progress. No significant differences in initial deviations of resorption and bone formation markers, peculiarities of calcium homeostasis were detected in “non respondents”. At the same time by the 12th month after treatment initiation the relationship between BMD increase with preservation of marked decrease of resorption marker (deoxypyridinoline) and bone formation marker (osteocalcin) was noted, that pointed out the expediency of prognostic model creation. Evaluation of the influence of certain risk factors (age, results of blood and urine biochemical tests, data of densitometry including the results of femoral neck BMD in some patients) using discriminant analysis showed that 81.5% of patients were correctly referred to the groups of patients who responded and not responded to treatment. Out of all initially studied parameters the most significant were 7 that in 78.6% of cases (method sensitivity) enabled to identify the patients with negative treatment effect and in 82.1% of cases (method specificity) - with positive treatment effect.

Radium 223 treatment in metastatic castrate-resistant prostate cancer: Impact of sequencing on survival—Real-world outcomes from a single United Kingdom center.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Xue Yan Jiang ◽  
Sarah Atkinson ◽  
Sam Cuming ◽  
Alexander Burns ◽  
Rachel Anne Pearson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Bone Metastasis ◽  
Systemic Treatment ◽  
Survival Outcomes ◽  
Prior Chemotherapy ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
The Impact

223 Background: Radium 223 (Ra-223) is a FDA and EMA approved alpha particle radiopharmaceutical used to treat men with metastatic castrate resistant prostate cancer (mCRPC) with symptomatic bone metastasis. In view of emerging systemic options, new EMA 2018 licence indication is for 3rd line onwards. We aim to evaluate the impact of systemic therapy sequencing on survival outcomes from a heterogeneous cohort of 228 patients treated with Ra-223 in a single UK centre. Methods: We prospectively collected data from 228 men underwent Ra-223 therapy for mCRPC between April 2014 and August 2018. Survival outcomes in relation to sequence of systemic treatment used prior to Ra-223 were analysed. Results: Medium age = 72 (51-87) years. Most patients (n = 142, 69%) received at least one systemic agent prior to Ra-223: docetaxel and/or cabaxitaxel chemotherapy (n = 60, 29%), abiraterone (n = 62, 30.1%) and enzalutamide (n = 67, 32.5%) in various sequences. No patients received concurrent Ra-223 /systemic treatment other than LHRH analogue. Key findings are summarized in table below. Conclusions: Our data demonstrated better survival trend in patients who received Ra-223 early. Patients who received prior chemotherapy have worse survival compared with those who were chemo-naïve likely due to bone marrow depletion. Ra-223 should not be offered to patients who have already had both cabaxitaxel and docetaxel as their medium survival is too poor to justify a treatment which takes 6 months to complete.[Table: see text]

Effects of Sodium Bicarbonate Ingestion on Anaerobic Performance: A Meta-Analytic Review

1993 ◽  
Vol 3 (1) ◽  
pp. 2-28 ◽  
Author(s):  
Larry G. Matson ◽  
Zung Vu Tran
Keyword(s):  
Sodium Bicarbonate ◽  
Treatment Effect ◽  
Anaerobic Exercise ◽  
Time To Exhaustion ◽  
Analytic Review ◽  
Positive Treatment Effect ◽  
Measured Time ◽  
Positive Treatment ◽  
Extracellular Environment ◽  
Induced Alkalosis

Many researchers have investigated the effects of induced metabolic alkalosis, by ingestion of sodium bicarbonate, on anaerobic exercise performance. But the results have been inconsistent and often contradictory. The purpose of this review was to synthesize the varied findings using a meta-analytic approach. Twenty-nine investigations met our inclusion criteria. Results show that, ingestion clearly results in a more alkaline extracellular environment. The dosage, however, was only moderately related to the increase in pH and HCO3-. Overall, performance was enhanced but the range of effect sizes was large, -0.12 to 2.87. In studies that measured time to exhaustion, there was a mean 27±20% increase in duration. The treatment effect, however, was only weakly related to the degree of induced alkalosis. But in comparing the 19 studies that showed a positive treatment effect with the 16 that showed no effect, the former were associated with a greater increase in pH following ingestion of a somewhat larger dosage, and a greater decrease in pH with exercise.

Low Participation Rates

2018 ◽  
pp. 62-70
Author(s):  
Dean Karlan ◽  
Jacob Appel
Keyword(s):  
Sample Size ◽  
Treatment Effect ◽  
General Public ◽  
Effective Sample Size ◽  
Random Assignment ◽  
Participation Rates ◽  
Intake Process ◽  
Positive Treatment Effect ◽  
Positive Treatment

This chapter focuses on low participation rates. Low participation rates squeeze the effective sample size for a test, making it more difficult, statistically, to identify a positive treatment effect. There are two moments in which low participation rates can materialize: during the intake process to a study or intervention, or after random assignment to treatment or control. Low participation during the intake process often occurs when marketing a program to the general public. Researchers working in the field with partner organizations often face inflexible constraints in trying to cope with low participation during intake. The second type of low participation—that which occurs after subjects have been randomly assigned to treatment or control—is a more daunting problem and is less likely solvable than low participation at the intake phase.

Correlation of increased eosinophil count following sipuleucel-T treatment with outcome in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4650-4650 ◽  
Author(s):  
Douglas G. McNeel ◽  
Daniel W. Lin ◽  
Thomas Gardner ◽  
Nadeem A. Sheikh ◽  
James Boyd Whitmore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hypereosinophilic Syndrome ◽  
Phase Iii ◽  
Cellular Immunotherapy ◽  
Cancer Specific Survival ◽  
Phase Iii Trials ◽  
Castrate Resistant ◽  
Humoral Responses ◽  
The Impact ◽  
Eosinophil Counts

4650 Background: Sipuleucel-T is the first autologous cellular immunotherapy approved for asymptomatic or minimally symptomatic mCRPC. In the IMPACT trial, pts treated with sipuleucel-T had transient increases in eosinophil counts compared with control. In this retrospective analysis, we assess potential correlations between eosinophilia, overall survival (OS), prostate cancer-specific survival (PCSS) and immune response following sipuleucel-T. Methods: Data from three phase III trials (D9901, D9902A, and IMPACT) were pooled. The analysis included CBCs performed at baseline and wks 2–34. Eosinophilia was defined as either >ULN (with normal baseline), or a max change from baseline within the top quartile, at any time between wks 2–16. Results: Increased eosinophil counts were seen in sipuleucel-T pts by wk 6, decreasing to near baseline by wk 14; eosinophil counts in control pts were stable. Of 377 sipuleucel-T pts eligible for analysis, 105 (27.9%) had eosinophilia. Baseline disease characteristics associated with eosinophilia were indicative of better prognosis (i.e., longer Halabi predicted survival [p=0.007], lower PSA [P=0.033], higher Hgb [p<0.001], and no prior docetaxel [p=0.012]). In univariate analyses, eosinophilia correlated with improved OS (HR=0.75; 95%CI: 0.56–1.01; p=0.057) and PCSS (HR=0.71; 95%CI: 0.53–0.97; p=0.031); trends persisted after adjusting for Halabi. The magnitude of eosinophilia positively correlated with antigen-specific humoral responses (p ≤0.039 for wks 6, 14 and 26) and elevations in the cytokines at wk 6 (IL2 [p=0.011], IL5 [p=0.038] and TARC [p=0.001]). AEs occurring more frequently (p<0.05) in pts with eosinophilia were infusion-related: pyrexia (33.3 v 21.3%) and nausea (19.0 v 10.7%). No cases of hypereosinophilic syndrome were reported. Conclusions: Increases in eosinophils after sipuleucel-T correlated with improved OS and PCSS. Large increases in eosinophil counts were associated with humoral responses and Th2-type cytokine production. Further studies of eosinophilia as a biomarker for sipuleucel-T response, particularly in earlier disease settings, are of interest.

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