The Experts below are selected from a list of 86325 Experts worldwide ranked by ideXlab platform
Luca Dezzani - One of the best experts on this subject based on the ideXlab platform.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase 3 COMPARZ study demonstrated non-inferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma (RCC). This COMPARZ Post Hoc Analysis characterized pazopanib responders, patient subgroups who achieved better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/day (N = 557) or sunitinib 50 mg/day, 4 weeks on/2 weeks off (N = 553). Secondary end-points include time to complete response [CR]/partial response [PR]; the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for pazopanib versus sunitinib (11.9 versus 17.4 weeks). A similar percentage of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). Within both arms, patients with adverse event (AE)-related dose modifications had higher cumulative doses, longer time on treatment, improved PFS and ORR, and more frequent AEs versus patients with no dose modification. Logistic regression analyses did not identify baseline characteristics associated with response in either arm. Conclusion These results support similar efficacy of pazopanib and sunitinib. Dose modifications when required due to AEs can be implemented safely without compromising pazopanib or sunitinib efficacy.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ Post Hoc Analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/d (n = 557) or sunitinib 50 mg/d, 4 weeks on/2 weeks off (n = 553). Secondary end points included time to complete response (CR)/partial response (PR); the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for patients treated with pazopanib versus sunitinib (11.9 vs. 17.4 weeks). Similar percentages of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). For patients without versus with adverse event (AE)-related dose reductions, median PFS, median overall survival, and ORR were 7.3 versus 12.5 months, 21.7 versus 36.8 months, and 22% versus 42% (all P Conclusion Dose modifications when required because of AEs were associated with improved efficacy, suggesting that AEs might be used as a surrogate marker of adequate dosing for individual patients.
Rachel S Skinner - One of the best experts on this subject based on the ideXlab platform.
-
prior human papillomavirus 16 18 as04 adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy Post Hoc Analysis from a randomized controlled trial
International Journal of Cancer, 2016Co-Authors: Suzanne M Garland, Jorma Paavonen, Unnop Jaisamrarn, Paulo Naud, Jorge Salmeron, Songnan Chow, Dan Apter, Xavier Castellsague, Julio Cesar Teixeira, Rachel S SkinnerAbstract:We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a Post-Hoc Analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomised (1:1) to receive vaccine or control at months 0, 1, and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present Post-Hoc Analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more Post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more Post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine=9,319; control=9,325), 454 (vaccine=190, control=264) underwent an excisional procedure during the trial. Efficacy 60 days or more Post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more Post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. This article is protected by copyright. All rights reserved.
Cora N Sternberg - One of the best experts on this subject based on the ideXlab platform.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase 3 COMPARZ study demonstrated non-inferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma (RCC). This COMPARZ Post Hoc Analysis characterized pazopanib responders, patient subgroups who achieved better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/day (N = 557) or sunitinib 50 mg/day, 4 weeks on/2 weeks off (N = 553). Secondary end-points include time to complete response [CR]/partial response [PR]; the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for pazopanib versus sunitinib (11.9 versus 17.4 weeks). A similar percentage of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). Within both arms, patients with adverse event (AE)-related dose modifications had higher cumulative doses, longer time on treatment, improved PFS and ORR, and more frequent AEs versus patients with no dose modification. Logistic regression analyses did not identify baseline characteristics associated with response in either arm. Conclusion These results support similar efficacy of pazopanib and sunitinib. Dose modifications when required due to AEs can be implemented safely without compromising pazopanib or sunitinib efficacy.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ Post Hoc Analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/d (n = 557) or sunitinib 50 mg/d, 4 weeks on/2 weeks off (n = 553). Secondary end points included time to complete response (CR)/partial response (PR); the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for patients treated with pazopanib versus sunitinib (11.9 vs. 17.4 weeks). Similar percentages of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). For patients without versus with adverse event (AE)-related dose reductions, median PFS, median overall survival, and ORR were 7.3 versus 12.5 months, 21.7 versus 36.8 months, and 22% versus 42% (all P Conclusion Dose modifications when required because of AEs were associated with improved efficacy, suggesting that AEs might be used as a surrogate marker of adequate dosing for individual patients.
Antony Loebel - One of the best experts on this subject based on the ideXlab platform.
-
insight and treatment outcomes in schizophrenia Post Hoc Analysis of a long term double blind study comparing lurasidone and quetiapine xr
Innovations in clinical neuroscience, 2017Co-Authors: Philip D Harvey, Antony Loebel, Cynthia O SiuAbstract:Objective: The objective of this Post-Hoc Analysis was to evaluate the effect of lurasidone and quetiapine extended-release (XR) on insight and judgment and assess the longitudinal relationships between improvement in insight and cognitive performance, functional capacity, quality of well-being, and depressive symptoms in patients with schizophrenia. Design: Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed-dose treatment with lurasidone 80mg, lurasidone 160mg, quetiapine XR 600mg, or placebo, followed by a long-term, double-blind, flexible-dose continuation study involving these agents. Results: Significantly greater improvement in insight and judgment (assessed by the Positive and Negative Syndrome Scale G12 item) for the lurasidone and quetiapine XR groups, compared to the placebo group, was observed at Week 6. Over a subsequent six-month continuation period, the flexible dose lurasidone group showed significantly greater improvement in insight from acute phase baseline compared to the flexible-dose quetiapine XR group (QXR-QXR) (p=0.032). Improvement in insight was significantly correlated with improvement in cognition (p=0.014), functional capacity (p=0.006, UPSA-B), quality of well-being (p=0.033, QWB), and depressive symptoms (p=0.05, Montgomery-Asberg Depression Rating Scale [MADRS] score) across treatment groups and study periods. Conclusion: In this Post-Hoc Analysis, flexibly dosed lurasidone 40 to 160mg/d was found to be associated with significantly greater improvement in insight compared to flexibly dosed quetiapine XR 200 to 800mg/d over long-term treatment in patients with schizophrenia. Across treatment groups, improvement in insight and judgment was significantly associated with improvement in cognition, functional capacity, quality of well-being, and depressive symptoms over time.
-
lurasidone for major depressive disorder with mixed features and anxiety a Post Hoc Analysis of a randomized placebo controlled study
Cns Spectrums, 2017Co-Authors: Joyce Tsai, Yongcai Mao, Andrei Pikalov, Daisy Ngmak, Michael E Thase, Antony LoebelAbstract:Objective The aim of this Post-Hoc Analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety. Methods The data in this Analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Asberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures. Results Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91). Conclusions In this Post-Hoc Analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.
-
lurasidone for major depressive disorder with mixed features and irritability a Post Hoc Analysis
Cns Spectrums, 2017Co-Authors: Alan C. Swann, Maurizio Fava, Joyce Tsai, Yongcai Mao, Andrei Pikalov, Antony LoebelAbstract:OBJECTIVE The aim of this Post-Hoc Analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability. METHODS The data in this Analysis were derived from a study of patients meeting DSM-IV-TR criteria for unipolar MDD, with a Montgomery-Asberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20-60 mg/d (n=109) or placebo (n=100). We defined "irritability" as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability. RESULTS Some 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (-22.6 vs. -9.5, p<0.0001, effect size [ES]=1.4) and without (-19.9 vs. -13.8, p<0.0001, ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (-1.4 vs. -0.3, p=0.0012, ES=1.0) and the YMRS disruptive-aggressive item (-1.0 vs. -0.3, p=0.0002, ES=1.2). CONCLUSIONS In our Post-Hoc Analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.
-
efficacy of lurasidone in adults aged 55 years and older with bipolar depression Post Hoc Analysis of 2 double blind placebo controlled studies
The Journal of Clinical Psychiatry, 2016Co-Authors: Martha Sajatovic, Joyce Tsai, Andrei Pikalov, Josephine Cucchiaro, Brent P Forester, H Kroger, Antony LoebelAbstract:Objective The aim of this Post Hoc Analysis was to evaluate the efficacy of lurasidone in patients aged 55 years and older with bipolar depression. Methods A Post Hoc Analysis was performed on the older adult subgroup (n = 142) of outpatients meeting DSM-IV-TR criteria for bipolar I depression in 2 placebo-controlled, 6-week, randomized, double-blind studies conducted from 2009-2012: a monotherapy study comparing fixed flexible-dose ranges of lurasidone 20-60 mg/d or 80-120 mg/d with placebo and an adjunctive therapy study comparing flexible doses of lurasidone 20-120 mg/d with placebo adjunctive to either lithium or valproate. The primary endpoint was mean change at week 6 in the Montgomery-Asberg Depression Rating Scale (MADRS) total score. Results In the randomized sample, the proportion of older adults was 88/505 (17.4%) in the monotherapy study and 54/348 (15.5%) in the adjunctive therapy study. In the older adult subgroup in the monotherapy study, mean change at week 6 in the MADRS was significantly greater for lurasidone versus placebo (-14.8 vs -7.1; P = .003; effect size, 0.83; pooled doses), and in the adjunctive therapy study, mean change for lurasidone was not significantly different from placebo (-13.9 vs -11.1; P = .398; effect size, 0.26). Discontinuation rates due to adverse events for lurasidone versus placebo were similar for the monotherapy (6.8% vs 6.9%) and adjunctive therapy (3.8% vs 7.1%) studies. Lurasidone had minimal effects on metabolic laboratory values. Conclusions The results of these Post Hoc analyses, which assessed the efficacy of lurasidone in older adults with bipolar disorder, found that monotherapy was significantly effective while adjunctive therapy was not associated with significant improvement. Both monotherapy and adjunctive therapy with lurasidone were safe and well-tolerated in this older adult population. Trial registration ClinicalTrials.gov identifiers: NCT00868699, NCT00868452.
-
lurasidone in the treatment of bipolar depression with mixed subsyndromal hypomanic features Post Hoc Analysis of a randomized placebo controlled trial
The Journal of Clinical Psychiatry, 2015Co-Authors: Roger S Mcintyre, Andrei Pikalov, Josephine Cucchiaro, H Kroger, Antony LoebelAbstract:Objective Mixed (subsyndromal hypomanic) features are prevalent in patients with bipolar depression and are associated with more severe and complex illness, including increased risk for suicide attempts, higher switch to mania during antidepressant therapy, and a higher rate of recurrence. The aim of this Post Hoc Analysis was to evaluate the efficacy and safety of lurasidone in the treatment of patients with bipolar depression presenting with mixed features. Method Patients with a DSM-IV-TR diagnosis of major depressive episode associated with bipolar I disorder, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 and a Young Mania Rating Scale (YMRS) score ≤ 12 were randomly assigned to 6 weeks of double-blind, once-daily treatment with lurasidone 20-60 mg, lurasidone 80-120 mg, or placebo. The presence of mixed features was defined as a YMRS score ≥ 4 at study baseline. Efficacy analyses included change in MADRS total score from baseline to week 6 (the primary outcome in the original study, conducted between April 2009 and February 2012). Results At baseline, mixed features were present in 56% of patients (lurasidone, n = 182/323; placebo, n = 90/162). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in MADRS scores in the mixed features group (-15.7 vs -10.9; P = .001; week 6; mixed model for repeated measures [MMRM]; effect size, 0.48) and in the group without mixed features (-15.2 vs -10.8; P = .002; week 6; MMRM; effect size, 0.48). Rates of protocol-defined treatment-emergent hypomania or mania were similar for patients with mixed features (lurasidone, 2.2%; placebo, 3.2%) and without mixed features (lurasidone, 3.4%; placebo, 0.0%). Conclusions Lurasidone was found in this Post Hoc Analysis to be efficacious in the treatment of patients with bipolar depression who present with mixed features (assessed cross-sectionally at study baseline). No increased risk of treatment-emergent mania was observed in either group. Trial registration ClinicalTrials.gov identifier: NCT00868699.
Robert J Motzer - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and correlative analyses of avelumab plus axitinib versus sunitinib in sarcomatoid renal cell carcinoma Post Hoc Analysis of a randomized clinical trial
ESMO Open, 2021Co-Authors: Toni K Choueiri, Robert J Motzer, J Larkin, Sumanta K Pal, Brian I Rini, Balaji Venugopal, B Alekseev, Hideaki Miyake, G Gravis, Mehmet Asim BilenAbstract:Background Among patients with advanced renal cell carcinoma (RCC), those with sarcomatoid histology (sRCC) have the poorest prognosis. This Analysis assessed the efficacy of avelumab plus axitinib versus sunitinib in patients with treatment-naive advanced sRCC. Methods The randomized, open-label, multicenter, phase III JAVELIN Renal 101 trial (NCT02684006) enrolled patients with treatment-naive advanced RCC. Patients were randomized 1 : 1 to receive either avelumab plus axitinib or sunitinib following standard doses and schedules. Assessments in this Post Hoc Analysis of patients with sRCC included efficacy (including progression-free survival) and biomarker analyses. Results A total of 108 patients had sarcomatoid histology and were included in this Post Hoc Analysis; 47 patients in the avelumab plus axitinib arm and 61 in the sunitinib arm. Patients in the avelumab plus axitinib arm had improved progression-free survival [stratified hazard ratio, 0.57 (95% confidence interval, 0.325-1.003)] and a higher objective response rate (46.8% versus 21.3%; complete response in 4.3% versus 0%) versus those in the sunitinib arm. Correlative gene expression analyses of patients with sRCC showed enrichment of gene pathway scores for cancer-associated fibroblasts and regulatory T cells, CD274 and CD8A expression, and tumors with The Cancer Genome Atlas m3 classification. Conclusions In this subgroup Analysis of JAVELIN Renal 101, patients with sRCC in the avelumab plus axitinib arm had improved efficacy outcomes versus those in the sunitinib arm. Correlative analyses provide insight into this subtype of RCC and suggest that avelumab plus axitinib may increase the chance of overcoming the aggressive features of sRCC.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase 3 COMPARZ study demonstrated non-inferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma (RCC). This COMPARZ Post Hoc Analysis characterized pazopanib responders, patient subgroups who achieved better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/day (N = 557) or sunitinib 50 mg/day, 4 weeks on/2 weeks off (N = 553). Secondary end-points include time to complete response [CR]/partial response [PR]; the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for pazopanib versus sunitinib (11.9 versus 17.4 weeks). A similar percentage of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). Within both arms, patients with adverse event (AE)-related dose modifications had higher cumulative doses, longer time on treatment, improved PFS and ORR, and more frequent AEs versus patients with no dose modification. Logistic regression analyses did not identify baseline characteristics associated with response in either arm. Conclusion These results support similar efficacy of pazopanib and sunitinib. Dose modifications when required due to AEs can be implemented safely without compromising pazopanib or sunitinib efficacy.
-
comparz Post Hoc Analysis characterizing pazopanib responders with advanced renal cell carcinoma
Clinical Genitourinary Cancer, 2019Co-Authors: Cora N Sternberg, Thomas E Hutson, Georg A Bjarnason, Viktor Grunwald, Christian Kollmannsberger, Paul Nathan, Camillo Porta, Robert J Motzer, Toni K Choueiri, Luca DezzaniAbstract:Abstract Background The phase III COMPARZ study showed noninferior efficacy of pazopanib versus sunitinib in advanced renal cell carcinoma. In this COMPARZ Post Hoc Analysis we characterized pazopanib responders, patient subgroups with better outcomes, and the effect of dose modification on efficacy and safety. Patients and Methods Patients were randomized to pazopanib 800 mg/d (n = 557) or sunitinib 50 mg/d, 4 weeks on/2 weeks off (n = 553). Secondary end points included time to complete response (CR)/partial response (PR); the proportion of patients with CR/PR ≥10 months and progression-free survival (PFS) ≥10 months; efficacy in patients with baseline metastasis; and logistic regression analyses of patient characteristics associated with CR/PR ≥10 months. Median PFS, objective response rate (ORR), and safety were evaluated in patients with or without dose reductions or interruptions lasting ≥7 days. Results Median time to response was numerically shorter for patients treated with pazopanib versus sunitinib (11.9 vs. 17.4 weeks). Similar percentages of pazopanib and sunitinib patients had CR/PR ≥10 months (14% and 13%, respectively), and PFS ≥10 months (31% and 34%, respectively). For patients without versus with adverse event (AE)-related dose reductions, median PFS, median overall survival, and ORR were 7.3 versus 12.5 months, 21.7 versus 36.8 months, and 22% versus 42% (all P Conclusion Dose modifications when required because of AEs were associated with improved efficacy, suggesting that AEs might be used as a surrogate marker of adequate dosing for individual patients.
