Sunitinib (SU) in patients with advanced, progressive pancreatic neuroendocrine tumors (pNET): Final overall survival (OS) results from a phase III randomized study including adjustment for crossover.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 309-309 ◽  
Author(s):  
Eric Raymond ◽  
Patricia Niccoli ◽  
Daniel Castellano ◽  
Juan W. Valle ◽  
Pascal Hammel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Proportional Hazards Model ◽  
Failure Time ◽  
Randomized Study ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Double Blind ◽  
Clinical Trial Information

309 Background: In 2010, the pivotal double blind Phase III study met its primary endpoint with a median progression-free survival (PFS) of 11.4 months (mo) for sunitinib vs. 5.5 mo for placebo (PBO) (HR=0.42; 95% CI 0.26-0.66; P <0.001) in patients (pts) with advanced, progressive pNET. This trial showed an OS difference favouring sunitinib (HR=0.41; 95% CI 0.19-0.89; P = 0.02). At 2 years since study closure, median OS was 33.0 mo for SU and 26.7 mo for PBO (HR=0.71; 95% CI 0.47-1.09; P = 0.115). Methods: A total of 171 pts were randomly assigned 1:1 to SU 37.5 mg continuous daily dose (n = 86) or PBO (n = 85). The primary end-point was investigator assessed PFS. Pts receiving PBO could crossover to SU at disease progression. Final OS at 5 years follow-up since study closure was analyzed using the Kaplan-Meier method and Cox proportional hazards model in the intent-to-treat (ITT) population. In addition, a series of methods were used to adjust for cross-over including rank-preserving structural failure time (RPSFT). Clinical trial information: NCT00428597 . Results: At 5 years follow-up since study closure, the median OS was 38.6 mo for those randomized to SU and 29.1 mo for those randomized to PBO (HR=0.73, 95% CI 0.50-1.06; P = 0.094). In total, 59 pts randomized to PBO (69%) crossed over to SU. OS results obtained applying methods to adjust for cross-over are shown in Table 1. Conclusions: The 5-year OS difference (9.5 mo) between SU and PBO is confirmed. Correction for crossover yielded a stronger OS advantage with SU, confirming that crossover likely confounded the OS results. Clinical trial information: NCT00428597. [Table: see text]

Placebo controlled, double blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID): Results on long-term survival.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4030-4030 ◽  
Author(s):  
Rudolf Arnold ◽  
Michael Wittenberg ◽  
Anja Rinke ◽  
Carmen Schade-Brittinger ◽  
Behnaz Aminossadati ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Proportional Hazards Model ◽  
Randomized Study ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Study Entry ◽  
Rank Test ◽  
Double Blind ◽  
Term Survival ◽  
Octreotide Lar

4030 Background: Octreotide LAR (O) compared to placebo (P) lengthens significantly time to tumor progression (TTP) in patients with metastatic midgut neuroendocrine tumors (Rinke et al. 2009). The antiproliferative response was more pronounced in patients with low (≤ 10%) hepatic tumor load (HL). To investigate whether this beneficial effect also affects overall survival (OS), patients included in the PROMID trial were followed until January 2013 at least once a year. Methods: Between July 2001 and January 2008, 42 and 43 patients were randomly assigned to receive O or P. Post study treatment was at the discretion of the local investigator. Data on cause of death and on post study treatment were documented. OS was analyzed using the Kaplan-Meier method. Treatment groups (O vs. P; HL at study entry ≤ 10% vs. >10%) were compared using the log rank test and hazard ratios were estimated with the use of the Cox proportional hazards model. Results: 41 of 85 patients died until January 2013. 19 in the octreotide and 22 in the placebo arm. Median OS for all 85 patients was 85 months, “not reached” in the O arm and 84 months in the P arm (p=0.59, HR=0.85 [CI 0.46; 1.56]). Cause of death was unrelated to the tumor disease in 8 patients. 26 of 64 patients (10 in the O vs. 16 in the P arm) died in the HL ≤ 10% subgroup and 15 of 21 patients (9 in the O vs. 6 in the P arm) in the HL > 10 % (p=0.002, HR=2.7). Median OS in the HL ≤ 10% subgroup was “not reached” (octreotide) vs 80.5 months (placebo) (p=0.14, HR=0.56 [CI 0.25; 1.23]). In the HL > 10% subgroup the respective numbers were 35 vs. 84 months (p=0.14, HR=2.18 [CI 0.75; 6.33]). Post study treatment in the O and P groups included octreotide LAR (29 vs. 38 patients), hepatic CHE (5 vs. 12 patients), PRRT (13 vs. 13 patients) and CHT (4 vs. 5 patients). Conclusions: Octreotide LAR not only prolongs TTP but also extends OS in the subgroup of patients with metastatic midgut NETs and a low HL (≤ 10% at study entry) but not in the high (HL > 10%) subgroup. Almost all patients who were randomized at study entry in the P group received octreotide LAR after disease progression, but these experienced a less favourable OS in the low HL subgroup. Clinical trial information: NCT00171873.

Updated overall survival (OS) results from the phase III MONALEESA-3 trial of postmenopausal patients (pts) with HR+/HER2- advanced breast cancer (ABC) treated with fulvestrant (FUL) ± ribociclib (RIB).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1001-1001
Author(s):  
Dennis J. Slamon ◽  
Patrick Neven ◽  
Stephen K. L. Chia ◽  
Guy Heinrich Maria Jerusalem ◽  
Michelino De Laurentiis ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Term Survival ◽  
Free Survival ◽  
Hazards Model

1001 Background: The Phase III MONALEESA-3 trial (NCT02422615) previously demonstrated a statistically significant improvement in OS with RIB, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i), plus FUL compared with placebo (PBO) plus FUL as first-line (1L) or second-line (2L) treatment in postmenopausal pts with HR+/HER2− ABC (median, not reached vs 40.0 mo; hazard ratio [HR], 0.72; 95% CI, 0.57-0.92, P =.00455). This analysis was final per the protocol; following the unblinding of the study, pts still on study treatment in the PBO arm were allowed to cross over to the RIB arm. We report an exploratory analysis of OS after an additional median 16.9 mo of follow-up, allowing for further characterization of long-term survival benefits of RIB. Methods: Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL in 1L and 2L settings. Updated OS was evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional postprogression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT), and CT-free survival were also evaluated and summarized. Results: At the data cutoff (Oct 30, 2020), the median follow-up was 56.3 mo (min, 52.7 mo) and 68 (14.0%) and 21 (8.7%) patients were still on treatment in the RIB vs PBO arms, respectively. With this extended follow-up, RIB + FUL continued to demonstrate an OS benefit vs PBO + FUL (median, 53.7 vs 41.5 mo; HR, 0.73; 95% CI, 0.59-0.90). RIB + FUL had prolonged OS vs PBO + FUL in the 1L (median, not reached vs 51.8 mo; HR, 0.64; 95% CI, 0.46-0.88) and 2L subgroups (median, 39.7 vs 33.7 mo; HR, 0.78; 95% CI, 0.59-1.04). Subgroup analyses also showed a consistent OS benefit compared with the intent-to-treat (ITT) population for most subgroups. PFS2, time to CT, and CT-free survival for the ITT population favored RIB + FUL (Table). Among pts who discontinued study treatment, 81.9% and 86.4% received a next-line subsequent antineoplastic therapy, while 14.0% and 30.0% received a CDK4/6i as any subsequent line in the RIB vs PBO arms, respectively. No new safety signals were observed. Conclusions: The previously demonstrated robust and clinically meaningful OS benefit with RIB + FUL compared with PBO + FUL was maintained after almost 5 years of follow-up in postmenopausal pts with HR+/HER2− ABC. The OS benefit of RIB was observed in the 1L and 2L subgroups, which further supports the use of RIB in these populations. The results also demonstrated a significant delay in the use of subsequent CT with RIB vs PBO. Clinical trial information: NCT02422615 .[Table: see text]

scholarly journals Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Maryam Farhadian ◽  
Sahar Dehdar Karsidani ◽  
Azadeh Mozayanimonfared ◽  
Hossein Mahjub
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Coronary Intervention ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Hazards Model ◽  
Cerebrovascular Events ◽  
Long Term Follow Up ◽  
Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

scholarly journals Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

2020 ◽  
Author(s):  
Yuko Yamaguchi ◽  
Marta Zampino ◽  
Toshiko Tanaka ◽  
Stefania Bandinelli ◽  
Yusuke Osawa ◽  
...  
Keyword(s):  
Older Adults ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Differentiation Factor ◽  
Hazards Model ◽  
Increased Risk ◽  
The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P&lt;.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

scholarly journals Clinical impact of regression from sustained to paroxysmal atrial fibrillation: the Fushimi AF registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Fujino ◽  
H Ogawa ◽  
S Ikeda ◽  
K Doi ◽  
Y Hamatani ◽  
...  
Keyword(s):  
Cardiac Death ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Clinical Impact ◽  
Cox Proportional Hazards Model ◽  
Cardiac Events ◽  
Hazards Model ◽  
Adverse Cardiac Events

Abstract Background Atrial fibrillation (AF) commonly progresses from paroxysmal type to sustained type in the natural course of the disease, and we previously demonstrated that the progression of AF was associated with increased risk of clinical adverse events. There are some patients, though less frequently, who regress from sustained to paroxysmal AF, but the clinical impact of the regression of AF remains unknown. Purpose We sought to investigate whether regression from sustained to paroxysmal AF is associated with better clinical outcomes. Methods Using the dataset of the Fushimi AF Registry, patients who were diagnosed as sustained (persistent or permanent) AF at baseline were studied. Conversion of sustained AF to paroxysmal AF during follow-up was defined as regression of AF. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, stroke, and hospitalization for heart failure (HF). Event rates were compared between the patients with and without regression of AF. In patients with sustained AF at baseline, predictors of MACE were identified using Cox proportional hazards model. Results Among 2,253 patients who were diagnosed as sustained AF at baseline, regression of AF was observed in 9.0% (202/2,253, 2.0 per 100 patient-years) during a median follow-up of 4.0 years. Of these, 24.3% (49/202, 4.6 per 100 patient-years) of the patients finally recurred to sustained AF during follow-up. The proportion of asymptomatic patients was lower in patients with regression of AF than those without (with vs without regression; 49.0% vs 69.5%, p&lt;0.01). The percentage of beta-blocker use at baseline was similar between the two groups (37.2% vs 33.8%, p=0.34). The prevalence of patients who underwent catheter ablation or electrical cardioversion during follow-up was higher in patients with regression of AF (catheter ablation: 15.8% vs 5.5%; p&lt;0.01, cardioversion: 4.0% vs 1.4%; p&lt;0.01, respectively). The rate of MACE was significantly lower in patients with regression of AF as compared with patients who maintained sustained AF (3.7 vs 6.2 per 100 patient-years, log-rank p&lt;0.01). Figure shows the Kaplan-Meier curves for MACE, cardiac death, hospitalization for heart failure, and stroke. In patients with sustained AF at baseline, multivariable Cox proportional hazards model demonstrated that regression of AF was an independent predictor of lower MACE (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.28 to 0.88, p=0.02), stroke (HR: 0.51, 95% CI: 0.30 to 0.88, p=0.02), and hospitalization for HF (HR: 0.50, 95% CI: 0.29 to 0.85, p=0.01). Conclusion Regression from sustained to paroxysmal AF was associated with a lower incidence of adverse cardiac events. Funding Acknowledgement Type of funding source: None

CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi51-vi51
Author(s):  
Kristen Batich ◽  
Duane Mitchell ◽  
Patrick Healy ◽  
James Herndon ◽  
Gloria Broadwater ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Recurrent Glioblastoma ◽  
Cox Proportional Hazards Model ◽  
Total N ◽  
Dc Vaccine ◽  
Dc Vaccines

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jian-jun Li ◽  
Yexuan Cao ◽  
Hui-Wen Zhang ◽  
Jing-Lu Jin ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Glucose Metabolism ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Significant Difference ◽  
Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

scholarly journals Incidence and Predictors of Hospitalization in Patients with Atrial Fibrillation: Results from the Chinese Atrial Fibrillation Registry Study

2020 ◽  
Author(s):  
Zhaojie Dong ◽  
Xin Du ◽  
Shangxin Lu ◽  
Chao Jiang ◽  
Shijun Xia ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Diseases ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Chronic Obstructive ◽  
Unique Identifier ◽  
Clinical Trial Registration

Abstract Background: Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which, however, has not been paid much attention in clinic. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients.Methods: From August 2011 to December 2017, 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were enrolled in this study. We described the incidence, causes of hospitalization according to age and gender categories. The Cox proportional hazards model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results: After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total frequency of hospitalizations); while patients aged 65-74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). Multivariate Cox model analysis verified the higher risk of hospitalization in patients complicated with heart failure (HF)[hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.08-1.24], established coronary artery disease (CAD) (HR 1.26, 95%CI 1.19-1.34), ischemic stroke/transient ischemic attack (TIA) (HR 1.26, 95%CI 1.18-1.33), diabetes (HR 1.16, 95%CI 1.10-1.22), chronic obstructive pulmonary disease (COPD) (HR 1.41, 95%CI 1.13-1.76), gastrointestinal disorder (HR 1.39, 95%CI 1.23-1.58), and renal dysfunction (HR 1.31, 95%CI 1.16-1.48). Conclusions: More than one-third of AF patients included in this study were hospitalized at least once during almost 3 years of follow-up. The main cause for hospitalization among elderly patients (≥65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated as strategies to reduce hospitalization in AF patients.Clinical Trial Registration: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

The Freestyle Valve in Severe Necrotizing Aortic Root Endocarditis: Comorbidity Upon Outcome

2021 ◽  
Author(s):  
Lorenz Hansen ◽  
Ann-Kathrin Ozga ◽  
Michael Klusmeier ◽  
Mathias Hillebrand ◽  
Aysun Tulun ◽  
...  
Keyword(s):  
General Population ◽  
Aortic Root ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Patch Repair ◽  
Patient Specific ◽  
Standardized Mortality Ratio ◽  
Term Outcome

Abstract Background Treatment of severe necrotizing aortic root endocarditis (SNARE) carries a substantial perioperative risk. As an alternative to homografts, we assessed short-term outcome and future prognosis in patients undergoing root replacement using the Freestyle valve. Methods Between 2000 and 2018, a total of 45 patients (mean age 70.9 ± 8.3 years, 66% men) underwent aortic root replacement for SNARE using the Freestyle valve. Mean Society of Thoracic Surgeons mortality score and EuroScore II were 22.6% ± 17.1 and 29.3% ± 20.9, respectively. Prosthetic endocarditis was present in 70.1%, and aortic annulus patch repair was performed in 64% of the patients. Median follow-up was 3.6 years (range: 0.1–14.5) and was 100% complete. Results The 30-day mortality was 15.5%. During follow-up, there were no reoperations, while reinfection was suspected in one patient. Survival was significantly inferior to the general population with a standardized mortality ratio of 10.7 (95% confidence interval [CI]: 9.1–12.6) (p < 0.0001). In 30-day survivors and after correction for significant comorbidities in a Cox proportional hazards model, estimated survival probabilities at 1, 5, and 10 years were 98.7 (95% CI: 92.5–99.8%), 94.1 (77.9–98.5%), and 63.8 (28.4–85.2%). Estimated mean difference in survival probability was better for the general population after postoperative year 6, but within the 95% CI for no difference. Conclusion Use of the Freestyle valve is reliable solution for the most complex cases with a low rate of reinfection. Early mortality is substantial and caused by the patient's condition and severity of the infection. Excess late mortality can be attributed to patient-specific comorbidities.

Post hoc analysis of the CLEAR study in advanced renal cell carcinoma (RCC): Effect of subsequent therapy on survival outcomes in the lenvatinib (LEN) + everolimus (EVE) versus sunitinib (SUN) treatment arms.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4562-4562
Author(s):  
Thomas E. Hutson ◽  
Toni K. Choueiri ◽  
Robert J. Motzer ◽  
Sun Young Rha ◽  
Anna Alyasova ◽  
...  
Keyword(s):  
Median Duration ◽  
Proportional Hazards Model ◽  
Objective Response ◽  
Anticancer Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
The Sun ◽  
Post Hoc ◽  
The Impact

4562 Background: The multicenter, open-label, randomized, phase 3 CLEAR study showed that LEN + EVE had a significant PFS benefit (HR 0.65, 95% CI 0.53-0.80, P<0.001) and improved objective response rate (relative risk 1.48, 95% CI 1.26-1.74) vs SUN in the first-line treatment of patients (pts) with advanced RCC. The difference in overall survival (OS) for LEN + EVE vs SUN was not statistically significant (HR 1.15, 95% CI 0.88-1.50) (Motzer R et al. NEJM. 2021). Post hoc subgroup analyses were performed to assess the impact of subsequent therapy on OS. Methods: Pts in the CLEAR study were randomly assigned (1:1:1) to 1 of 3 treatment arms, including LEN 18 mg + EVE 5 mg once daily (QD) and SUN 50 mg QD (4 weeks on then 2 weeks off). These post hoc analyses examined OS by subsequent systemic anticancer medication in the LEN + EVE and SUN arms. Hazard ratios (HR; LEN + EVE vs SUN) were based on stratified (geographic region and MSKCC prognostic risk groups) Cox proportional hazards model. Results: Among 1069 pts with advanced RCC randomized in the CLEAR study, 714 pts were randomly assigned to the LEN + EVE and SUN arms (N=357/each). The median duration of survival follow-up was 27 months in the LEN + EVE arm and 26 months in the SUN arm. Given the shorter median duration of study treatment with SUN (7.8 months) vs LEN + EVE (11.0 months), more pts in the SUN arm received subsequent anticancer therapy during survival follow-up (LEN + EVE, n=167; SUN, n=206). Among pts who received subsequent therapy, pts in the LEN + EVE arm had a longer median time from randomization to initiation of subsequent therapy vs those in the SUN arm (8.0 vs 6.6 months, respectively). OS for the overall population, for pts with no subsequent anticancer therapy, and for pts with no subsequent immunotherapy is shown in the table. In the US population subgroup (LEN + EVE, n=62; SUN, n=61) of the CLEAR study, in which a similar number of pts received subsequent systemic anticancer therapies in the LEN + EVE vs SUN arms (62.9% vs 65.6%, respectively), OS was comparable among the 2 arms (HR 0.95, 95% CI 0.51-1.76). Overall, the safety profile was consistent with the known safety profiles of LEN + EVE and SUN. In both arms, most treatment-emergent deaths were due to progressive disease; there were few treatment-related deaths (<1%, per arm) and no clustering of events. Conclusions: In the CLEAR study, LEN + EVE met the primary endpoint of a significant benefit in PFS vs SUN. The results of these exploratory analyses suggest that subsequent systemic anticancer therapy affected the OS outcome results for LEN + EVE vs SUN in the CLEAR study. Clinical trial information: NCT02811861. [Table: see text]

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