Biomarker analysis from a phase III trial (GOLD) of dovitinib (Dov) versus sorafenib (Sor) in patients with metastatic renal cell carcinoma after one prior VEGF pathway–targeted therapy and one prior mTOR inhibitor therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 473-473 ◽  
Author(s):  
Bernard J. Escudier ◽  
Camillo Porta ◽  
Matthew Squires ◽  
Cezary Szczylik ◽  
Christian K. Kollmannsberger ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Plasma Samples ◽  
Plasma Biomarkers ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Biomarker Analysis ◽  
Line Setting

473 Background: In the GOLD trial, Dov did not improve progression-free survival (PFS) or overall survival (OS) over Sor. An exploratory objective of the study was to investigate plasma and tumor biomarkers to predict outcome. Methods: Plasma samples were obtained longitudinally throughout the study, and biomarkers were assessed by immunoassay. Primary archival tumor samples were assessed by immunohistochemistry. Log-rank tests, stratified by baseline MSKCC risk group, for difference in Kaplan-Meier curves between biomarker category (low/high based on </≥ median baseline values) within treatment arm were performed. Hazard ratios (HRs) were estimated from Cox proportional hazards models. Results: Plasma samples were available from 561 patients (Dov, n = 281; Sor, n = 280), and tumor samples were available from 341 patients (Dov, n = 181; Sor, n = 160). Baseline plasma biomarker levels were not predictive of Dov or Sor PFS or OS. However, strong prognostic effects, particularly for OS, were observed. High baseline cKIT and low baseline FGF2, HGF, PlGF, sVEGFR1, VEGFA, and VEGFD were associated with better OS for both Dov and Sor (Table). Changes from baseline in a number of plasma biomarkers were observed following treatment with Dov and Sor, consistent with VEGFR/FGFR inhibitory effects. Prognostic effects were also observed for low FGFR2 (PFS) and low FGF2 (OS) expression in archival tumors. Conclusions: Baseline plasma biomarkers are prognostic but not predictive in the third-line setting. Clinical trial information: NCT01223027. [Table: see text]

Efficacy of the hypomethylating agents as frontline, salvage, or maintenance therapy among older adults with acute myeloid leukemia (AML).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18002-e18002
Author(s):  
Bernard Tawfik ◽  
Sarunas Sliesoraitis ◽  
Heidi D. Klepin ◽  
Julia Lawrence ◽  
Scott Isom ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Proportional Hazards ◽  
Response Rates ◽  
Cox Proportional Hazards ◽  
Hypomethylating Agents ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Comorbidity Burden ◽  
Line Setting

e18002 Background: The hypomethylating agents, azacitidine and decitabine, have emerged as an alternative to initial and salvage therapy in patients with AML. Little is known about how AML responds to hypomethylating agents after standard therapy and the use of these agents in the treatment of AML is currently evolving. Methods: We retrospectively examined 76 consecutive AML patients ≥60 years old treated with hypomethylating agents at Wake Forest from 2002-2009 as either 1st-line therapy (n=35), salvage (n=28) or consolidation (n=13). We collected data on age, gender, race, Charleston Comorbidity index (CCI), cytogenetics, type of treatment, Complete Remission (CR), Complete Remission with incomplete count recovery (CRi), and survival. Statistical analysis was performed using Kaplan-Meier estimates and cox proportional hazards models. Results: In the front line setting 11.4% of patients received azacitidine (AZA), 34.3% received 5 days of decitabine (5DD) and 54.3% received 10 days (10DD). In the salvage cohort 3.6% received AZA, 42.8% received 5DD and 53.6% received 10DD. In the consolidation cohort 18.2% received AZA and 81.8% received 5DD. Response rates (CR+CRi) were reduced in the salvage cohort compared to frontline (3.6% versus 25.7%, p=0.033). Despite the reduced response rate, overall survival in the two cohorts was similar when survival was calculated from time of hypomethylating agent (8.2 [CI 4.8-10.3] vs. 3.1 [CI 1.9-12.0] months, p = 0.2967). In the salvage cohort overall survival from the time of relapse was similar to the overall survival of those treated in 1st consolidation (18.3 [CI 15.1 -23.5] vs. 13.7 [CI 8.0 – 21.6] months, p= 0.3346). This suggests that hypomethylating agents given in first remission did not improve survival over patients who received them only after relapse. Comorbidity burden (by the CCI) showed a non-significant trend with prognosis (p= 0.0667). Conclusions: These data suggest prior cytotoxic therapy decreases marrow response rates to hypomethylating agents but not survival. Furthermore, use of hypomethylating agents for consolidation did not result in an increase in median overall survival when compared to their use in salvage.

scholarly journals Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1040
Author(s):  
Valérie Gounant ◽  
Michael Duruisseaux ◽  
Ghassen Soussi ◽  
Sylvie Van Hulst ◽  
Olivier Bylicki ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Cox Proportional Hazards ◽  
Poor Performance Status ◽  
Low Grade ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models

Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy.

Association of early bone metastases and outcomes of the bone predominant metastatic urothelial carcinoma (BP mUC) phenotype.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16016-e16016
Author(s):  
Ariel Ann Nelson ◽  
Matthew David Wright ◽  
Ali Raza Khaki ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Ravi Kumar Kyasaram ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Proportional Hazards ◽  
De Novo ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
First Line ◽  
Kaplan Meier ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting ◽  
Line Setting

e16016 Background: Prior analyses demonstrated worse outcomes with the BP mUC clinical phenotype. UC molecular subtypes that may correlate with the BP phenotype have been defined, however molecular subtyping is not a readily available standard practice. We hypothesized that BP mUC has worse prognosis vs. non-BP (NBP) mUC and evaluated patient (pt) characteristics associated with the mUC subtype, responses and outcomes. Methods: We searched the electronic medical record (EMR) to identify pts with mUC who received systemic therapy in the metastatic setting. Demographic, clinicopathologic, treatment (trt), response, progression-free survival (PFS), overall survival (OS ) from start of first line trt. Imaging was reviewed to identify NBP or BP disease. Logistic regression, Cox proportional-hazards and Kaplan-Meier analyses were performed. Results: 149 mUC pts were identified (64% male, 68% smokers ), median age at 1st line trt was 68 years. 70% had de-novo mets, 46% to lung and 27% to liver. 22% of pts were BP, of these, 36% were de-novo metastatic. In non- de-novo metastatic pts (70% of pts), first progression of disease to bone was associated with development of the BP phenotype (OR = 30.46, 95% CI 6.37 to 145.61; p < 0.0001). BP pts had higher rate of death (HR = 2.28, 95% CI 1.45 to 3.58, p = 0.0004), shorter PFS from 1st line trt, (11.7 vs 14.9 weeks, p = 0.032) as well as shorter OS from 1st line trt (24.6 vs 56.6 weeks, p = 0.002) compared to NBP pts. There was no difference in PFS between BP and NBP groups for pts treated with 1st line platinum-based chemotherapy (11.8 vs 18.3 weeks, p = 0.091) or for BP pts treated with 1st line immunotherapy vs platinum-based chemotherapy (11.71 vs 11.86 weeks, p = 0.135). Conclusions: Early bone metastases are associated with the development of the BP metastatic phenotype. BP pts have worse PFS and OS from 1st line trt compared to NBP pts. PFS remains poor when BP pts are treated with either platinum-based chemotherapy or immunotherapy in the first line setting. Imaging to determine the presence of bone metastases may routinely be pursued and careful attention paid on follow up imaging. Clinical trials and prospective registries focusing on efficacy endpoints for BP mUC are needed.

Sunitinib in patients with pancreatic neuroendocrine tumors (panNETs): Exploratory pharmacogenomic analyses.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 255-255
Author(s):  
Nicola Fazio ◽  
Jean-Francois Martini ◽  
Adina-Emilia Croitoru ◽  
Michael Schenker ◽  
Sherry Li ◽  
...  
Keyword(s):  
Protein Transport ◽  
Proportional Hazards ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Nucleotide Polymorphisms ◽  
Exact Test ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve

255 Background: In a phase IV trial (NCT01525550), median progression-free survival (PFS) was 13.2 mo in sunitinib-treated patients (pts) with well-differentiated panNETs. Objective response rate (ORR) was 24.5% and median overall survival (OS) was 37.8 mo. Exploratory analyses evaluated potential associations between single nucleotide polymorphisms (SNP) in genes involved in angiogenesis, protein transport or inflammatory response and clinical outcomes. Methods: Blood samples were genotyped using TaqMan assays for 12 SNPs previously associated with panNET risk, prognosis or drug effect. Associations between SNP and PFS or OS were assessed by comparing genotypes within treatment-naïve (TN), previously treated (PT) and combined groups, and within a genotype between treatment groups, using Kaplan-Meier analysis and Cox proportional hazards models. Fisher’s exact test was used for association between ORR and genotype. PFS and ORR were investigator-assessed. P values displayed are unadjusted and Bonferroni method was used for multiplicity adjustment. Results: 56 pts were genotyped: 25 TN and 31 PT. There were no significant associations between genotype and PFS or OS but there was a trend toward shorter PFS in pts with VEGFR1 rs9554320 C/A versus C/C (hazard ratio [HR] 1.78; 95% confidence interval [CI] 0.83–3.82; p = 0.117) and VEGFR1 rs9582036 A/C versus A/A (HR 1.88; 95% CI 0.9–3.93; p = 0.102). The genotypes G/G of VEGFA rs2010963 (p = 0.041) , G/G of VEGFA rs833068 (p = 0.041) and A/C of VEGFR1 rs9582036 (p = 0.046) showed a trend toward a higher ORR in the PT versus TN group. Genotype T/T of VEGFR2 rs7692791 (p = 0.103) showed a trend toward to a lower ORR in the TN versus PT group. Higher ORR was associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p = 0.001) in the combined group. Conclusions: Potential associations between ORR and VEGFA rs2010963 and rs833068, VEGFR1 rs9582036 and VEGFR2 rs7692791 were observed. IL1B rs16944 was significantly associated with ORR, consistent with the role of IL1B in panNET etiology and development. Most correlations were not significant after adjustment for multiplicity. Clinical trial information: NCT01525550.

scholarly journals Clinical outcomes in patients with metastatic renal cell carcinoma receiving everolimus or temsirolimus after sunitinib.

2014 ◽  
Vol 8 (3-4) ◽  
pp. 121 ◽  
Author(s):  
Roberto Iacovelli ◽  
Giacomo Cartenì ◽  
Michele Milella ◽  
Rossana Berardi ◽  
Giuseppe Di Lorenzo ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Clinical Activity ◽  
Second Line ◽  
Cox Proportional Hazards Models ◽  
Line Setting

Introduction: There are little data on the clinical activity of temsirolimus (TM) and everolimus (EV) when used as second-line therapy after sunitinib (SU) in patients with metastatic renal cellcarcinoma (mRCC).Methods: Patients with mRCC treated with EV or TM after SU were included in this retrospective analysis. Progression-free survival (PFS), time to sequence failure (TTSF) from the start of SU to disease progression with EV/TM and overall survival (OS) were estimated using Kaplan-Meier method and compared across groups using the log-rank test. Cox proportional hazards models were applied to investigate predictors of TTSF and OS.Results: In total, 89 patients (median age 60.0 years) were included. At baseline 43% were classified as MSKCC good-risk, 43% as intermediate-risk and 14% as poor-risk. Median OS was 36.3 months and median TTSF was 17.2 months. Sixty-five patients received SU-EV and 24 patients SU-TM. Median PFS after the second-line treatment was 4.3 months in the EV group and 3.5 months in the TM group (p = 0.63). Median TTSF was 17.0 and 18.9 months (p = 0.32) and the OS was 35.8 and 38.3 months (p = 0.73) with SU-EV and SU-TM, respectively. The prognostic role of initial MSKCC was confirmed by multivariable analysis (hazard ratio 1.76, 95% confidence interval 1.08-2.85. p = 0.023).Conclusions: This study did not show significant differences in terms of disease control and OS between EV and TM in the second-line setting. EV remains the preferred mTOR inhibitor for the treatment of mRCC patients resistant to prior tyrosine kinase inhibitor treatment.

Outcomes of patients (pts) with metastatic renal cell carcinoma (mRCC) treated with pazopanib after progression on other targeted therapies (TT): A single-institution experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4615-4615
Author(s):  
Marc Ryan Matrana ◽  
Aditya V. Shetty ◽  
Bradley J. Atkinson ◽  
Lianchun Xiao ◽  
Paul G. Corn ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Kinase Inhibitor ◽  
Multivariable Analysis ◽  
Safety Data ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Treatment Naïve ◽  
Metastatic Sites

4615 Background: Pazopanib is an approved multi-tyrosine kinase inhibitor that prolongs progression-free survival (PFS) compared to placebo in treatment-naive and cytokine-refractory mRCC. Outcomes and safety data on its use after TT are limited. Methods: We retrospectively reviewed pts with mRCC who received salvage pazopanib between 11/09-11/11. Kaplan-Meier method was used to estimate survival outcomes. PFS was calculated from start of pazopanib until progressive disease (PD) or death. Univariable and multivariable Cox proportional hazards models were fitted to evaluate associations of PFS with covariables. Results: 114 consecutive pts met inclusion criteria (median age 62.6 years, 66% males, 83% clear cell). All pts had PD after other TT (median # of prior TT 2, range 1-5; median time on prior TT 23.3 mos). 79% of pts had PD on sunitinib, 39% on sorafenib, 19% on temsirolimus, 59% on everolimus, and 23% on bevacizumab. 25% received prior chemotherapy and 16% received prior cytokines in addition to TT. 87% had prior nephrectomy. 11% had favorable-risk, 68% intermediate-risk, and 21% poor-risk per MSKCC criteria. 85 events (PD or death) occurred. Median OS was 17 mos (95% CI: 10.3-NA). Median PFS was 6.4 mos (95% CI: 4.5-9.5). By multivariable analysis, PFS was associated with male gender (HR=0.433, 95%CI: 0.269-0.696; p=0.0006), # of metastatic sites (HR=1.252; 95%CI: 1.04-1.503; p=0.016), hypertension exacerbation (HR=0.378; CI: 0.175-0.813; p=0.0128) and PS 2+ vs.0-1 (HR=2.067; CI: 1.243-3.437; p=0.0052). 58% discontinued pazopanib due to PD, 12% died of PD on treatment, and 11% discontinued pazopanib due to adverse events (AEs), mostly GI complaints or fatigue. There were no treatment related deaths. Common AEs included: fatigue (44%), diarrhea (29%), nausea/vomiting (15%), anorexia (14%), hypertension exacerbation (11%), hypothyroidism (11%), hand-foot skin reaction (9%), and increase LFTs (4%). 86% of AEs were grade 1/2. Conclusions: In this retrospective study, pazopanib demonstrated efficacy in mRCC following PD with other TT. AEs were mild/moderate and manageable.

Real-world (RW) outcomes for advanced non-small cell lung cancer (aNSCLC) patients (pts) with EGFR exon 19 deletions (x19del) stratified by deletion size.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9591-9591
Author(s):  
Sai-Hong Ignatius Ou ◽  
Russell Madison ◽  
Tamara Snow ◽  
Jeremy Snider ◽  
Margaret Elizabeth McCusker ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Comprehensive Genomic Profiling ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Egfr Tki ◽  
Egfr Tkis

9591 Background: EGFR x19dels are well-established targetable drivers in NSCLC. Historically x19dels have been treated as a single group, but it’s unclear whether responses vary for distinct subtypes. We compared demographic, clinical and genomic characteristics as well as outcomes to EGFR tyrosine kinase inhibitors (TKIs) for aNSCLC pts with x19dels of varying lengths using a RW Clinico-Genomic Database (CGDB). Methods: Eligible pts had a diagnosis of aNSCLC, received care within the Flatiron Health network between 1/2011-9/2019, and had comprehensive genomic profiling (CGP) by Foundation Medicine. Clinical characteristics, treatment history and RW progression were obtained via technology-enabled abstraction as previously described (Singal G, JAMA 2019). x19del length was evaluated for association with overall survival (OS) and RW progression-free survival (rwPFS) with Kaplan-Meier analysis and unadjusted/adjusted (practice type, gender, age at TKI start, EGFR TKI type, race) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Among 6,577 aNSCLC pts, EGFR x19dels were detected in 336 cases (5%). E746_A750del was the most frequent (214; 64%) and generally 5 amino acid (aa) deletions (x19del-5) were the most common (241; 72%). Other deletions (x19del-other) of 6 (61; 18%), 3 (20; 6%), 4 (11; 3%) or 8 aa (3; 1%) were also observed. Among pts treated with 1st-line EGFR TKI monotherapy after CGP, the x19del-5 (n = 70) cohort was more frequently female compared to x19del-other (n = 27) (90% vs 59%, p = 0.001). No statistically significant differences in the frequency of co-occurring alterations were observed, specifically for genes associated with response to EGFR TKI response such as CTNNB1 (14% vs 19%) and PIK3CA (10% vs 15%). 1st line EGFR TKIs used were similar for x19del-5 vs x19del-other (43% vs 41% osimertinib, 30% vs 37% erlotinib, 24% vs 22% afatinib, 3% vs 0% gefitinib). x19del-5 pts had similar median rwPFS (10.6 vs 10.6 months, HR: 0.73 [0.41-1.28], aHR:0.78 [0.38-1.59]) and median OS (29.2 vs 24.9 months, HR: 0.64 [0.32- 1.29], aHR: 0.75 [0.32-1.75]) compared to x19del-other. Conclusions: In a RW CGDB of 336 aNSCLC pts with EGFR x19dels, 5 aa x19dels were most common (71%) and 29% of cases had 3, 4, 6 or 8 aa x19dels . For pts included in the treatment cohort, no significant differences in rwPFS or OS were observed. These results suggest that x19del length does not significantly impact clinical outcomes to 1st-line EGFR TKIs.

Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Kochav ◽  
R.C Chen ◽  
J.M.D Dizon ◽  
J.A.R Reiffel
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Class I ◽  
Class Iii ◽  
Bundle Branch Block ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Hazard Ratios ◽  
History Of ◽  
Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

2022 ◽  
Author(s):  
Samo Rozman ◽  
Nina Ružić Gorenjec ◽  
Barbara Jezeršek Novaković
Keyword(s):  
Hodgkin Lymphoma ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Relative Dose Intensity ◽  
Cox Proportional Hazards Models ◽  
Stage Disease ◽  
Stage Iv Disease

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

scholarly journals Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice

2017 ◽  
Vol 117 (06) ◽  
pp. 1072-1082 ◽  
Author(s):  
Xiaoyan Li ◽  
Steve Deitelzweig ◽  
Allison Keshishian ◽  
Melissa Hamilton ◽  
Ruslan Horblyuk ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Real World ◽  
Proportional Hazards ◽  
Significant Risk ◽  
Haemorrhagic Stroke ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Cox Proportional Hazards Models ◽  
Warfarin Treatment

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

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