Months For Pazopanib Research Articles

An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the 'Pamerit' study.

Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan-Meier curves, log-rank test and multivariable Cox's models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4months, respectively, significantly correlating with International Metastatic RCC Database Consortium's good prognosis (P<0.001), ECOG PS 0 (P<0.001), age (<75years, P=0.005), surgery (P<0.001) and response to pazopanib (P<0.001). After 3months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium's favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium's favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium's good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

Real-World Evidence Data on Metastatic Renal-Cell Carcinoma Treatment in Austria: The RELACS Study.

Treatment decisions in routine clinical practice are based on reports of clinical trials, which represent highly selected populations. Limited studies reported real-world evidences representing routine clinical practices in patients with renal-cell carcinoma (RCC) in Europe. The aim of this retrospective, noninterventional chart review was to collect data on the treatment landscape for patients with advanced/metastatic RCC in routine clinical practice in a broader patient population in Austria. Patients with advanced/metastatic RCC receiving systemic treatment between June 2010 and June 2016 across 12 centers in Austria were included. Parameters were entered into an electronic case report form from the participating sites via the application Hermesoft electronic data capture system. Progression-free survival (PFS) and overall survival (OS) were the 2 primary end points. The median PFS and OS were 12 months and 44 months, respectively (first-line PFS was 14 months for pazopanib and 13 months for sunitinib; first-line OS was 44 months for pazopanib and 48 months for sunitinib). Factors influencing the OS were sex, with female patients at a significantly higher risk than male patients (hazard ratio= 1.719), Eastern Cooperative Oncology Group performance status > 0 increased the risk twice (hazard ratio= 2.048), and number of metastases > 3 before the first line doubled the risk compared to metastases (hazard ratio= 2.064). OS in this retrospective chart review was considerably longer than the previous reports in real-world patients, underlining the benefit of current RCC treatment options in routine clinical practice.

Assessment of potential predictive value of peripheral blood inflammatory indexes in 26 cases with soft tissue sarcoma treated by pazopanib: a retrospective study.

PurposeThe aim of this study was to evaluate the prognostic and predictive value of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (DNLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in soft tissue sarcoma (STS) cases treated with pazopanib.Materials and methodsThe study population included 26 STS cases treated with pazopanib for at least 3 months. NLR, DNLR, LMR, and PLR were evaluated at baseline, and at third month of therapy and also compared with response to pazopanib. Median measurements were taken as cutoff for NLR (4.8), DNLR (3.1), LMR (3.6), and PLR (195). The associations between these cutoff values and survival times (progression-free survival [PFS] and overall survival [OS]) were assessed by Kaplan–Meier curves and Cox proportional models.ResultsPatients with low pretreatment NLR and DNLR had longer OS (P=0.022, P=0.018), but low PLR was found to be associated only with longer OS. Additionally, decrease in NLR and DNLR after 3 months of therapy as compared with pretreatment measurements was found to be associated with an advantage for OS (P=0.021, P=0.010, respectively) and PFS (P=0.005, P=0.001, respectively). Response to pazopanib; changes in NLR, DNLR, LMR, and PLR; and >3 metastatic sites were found to be independent risk factors in univariate analysis, but NLR was the only independent risk factor in multivariate analysis.ConclusionLow pretreatment and decrease in NLR and DNLR values, and regression/stable disease after 3 months of pazopanib are predictive factors for longer OS and PFS.

Analysis of Efficacy and Toxicity Profile of First-Line Sunitinib or Pazopanib in Metastatic Clear Cell Renal Cell Carcinoma in the Brazilian Population.

PurposeSunitinib and pazopanib are multitargeted tyrosine kinase inhibitors (TKIs) that act against vascular endothelial growth factor receptors and are standard first-line treatment options for metastatic clear cell renal cell carcinoma (ccRCC). The Brazilian public health system diverges from the randomized clinical trials in the availability of first and subsequent lines of treatment and in clinical and demographic characteristics of patients. Therefore, it is essential to describe the history of advanced ccRCC during and after TKI treatment in this population.MethodsWe performed a retrospective analysis of patients with advanced ccRCC treated with a first-line TKI (either sunitinib or pazopanib) between February 2009 and March 2017 in a single academic Brazilian cancer center (Instituto do Câncer do Estado de São Paulo).ResultsOf the 222 patients, 109 were treated with sunitinib and 113 with pazopanib. The median duration of treatment and overall survival (OS) were 6.4 and 15.2 months for sunitinib and 6.7 and 14.2 months for pazopanib, respectively. Discontinuation of treatment occurred secondarily to progressive disease or death in 64.2% of patients using sunitinib and in 54.8% of patients using pazopanib. Adverse events were responsible for discontinuation of treatment in 28.4% of patients in the sunitinib group and in 22.1% in the pazopanib group. According to Memorial Sloan-Kettering Cancer Center risk categories, the OS was 32.9 months, 15.9 months, and 8.1 months for low risk, intermediate risk, and poor risk, respectively (hazard ratio, 1.72; 95% CI, 1.13 to 2.26; P < .001).ConclusionThe use of TKI inhibitors as first-line treatment of metastatic RCC is effective and feasible in the Brazilian public health. However, the median OS of our population is considerably lower compared with the prospective trials that evaluated the same drugs.

Paclitaxel With and Without Pazopanib for Persistent or Recurrent Ovarian Cancer

Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States. Pazopanib is an oral, multitarget kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptors α and β; and proto-oncogene receptor tyrosine kinase (c-KIT). To estimate the progression-free survival (PFS) hazard ratio (HR) of weekly paclitaxel and pazopanib compared with weekly paclitaxel and placebo in women with recurrent ovarian cancer. Secondary objectives included frequency and severity of adverse events, proportion responding, and overall survival (OS) in each arm. Translational research objectives included exploring the association between possible biomarkers and single-nucleotide polymorphisms in vascular endothelial growth factor A, interleukin 8, and hypoxia-inducible factor 1α; and PFS, OS, and proportion responding. A randomized, placebo-controlled, double-blind phase 2 study was conducted at 26 participating institutions. Patients were enrolled between December 12, 2011, and April 22, 2013. Data were frozen on August 11, 2014. Participants were patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1 to 3 prior regimens and performance status of 0 to 2. One hundred six patients enrolled; 100 were evaluable for toxic effects. All patients received paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 28 days and were randomized 1:1 to pazopanib 800 mg orally daily or placebo. The primary end point was PFS. The study was designed to detect a 37.5% reduction in the hazard with 80% power (α = 10%). A total of 106 women (median age [range], 61 [35-87] years; 88 [83%] white) were enrolled. Study arms were well balanced for age, performance status, measurable disease, and prior bevacizumab. Proportion responding was 14 of 44 (31.8%) vs 10 of 44 (22.7%) for pazopanib plus paclitaxel vs paclitaxel alone. Median PFS was 7.5 vs 6.2 months for pazopanib plus paclitaxel vs paclitaxel alone, respectively (HR, 0.84; 90% CI, 0.57-1.22; P = .20). Median OS was 20.7 vs 23.3 months for pazopanib plus paclitaxel vs paclitaxel alone (HR, 1.04; 90% CI, 0.60-1.79; P = .90). Severe hypertension was more common on the pazopanib plus paclitaxel arm (relative risk, 12.0; 95% CI, 1.62-88.84). More patients discontinued treatment on the paclitaxel arm for disease progression (34 of 52 [65.4%] vs 17 of 54 [31.5%]), and more on the pazopanib plus paclitaxel arm for adverse events (20 of 54 [37%] vs 5 of 52 [9.6%]). No association was found between single-nucleotide polymorphisms (interleukin 8 and hypoxia-inducible factor 1α) and OS and proportion responding. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype, with 1 of 14 (7%), 3 of 15 (20%), and 4 of 8 (50%) responding, respectively. The combination of pazopanib plus paclitaxel is not superior to paclitaxel in women with recurrent ovarian cancer. clinicaltrials.gov Identifier: NCT01468909.

PLUTO: A randomised phase II study of pazopanib versus paclitaxel in relapsed urothelial tumours.

430 Background: Two previous single arm trials have drawn conflicting conclusions regarding pazopanib in urothelial bladder cancers (UBC) after failure of platinum-based chemotherapy. PLUTO is a randomized phase II trial to compare the efficacy of pazopanib with paclitaxel in this setting. Methods: It was planned for 140 patients with progressive, advanced UBC (with at least a component of transitional cell carcinoma) who had previously received a single prior platinum containing chemotherapy regimen for advanced UBC to be randomised(1:1). Patients in arm A received weekly paclitaxel 80mg/m2 and those in arm B received pazopanib (800mg once daily) until progression. The primary endpoint was overall survival analysis of which would occur after 110 events. The efficacy was assessed by an independent data monitoring committee during the trial. Results: Between Aug 2012- Oct 2014, 131 patients were randomised. 74.0% of patients had visceral metastases. The study was terminated early by the IDMC due to futility of pazopanib. Final analysis after 110 deaths occurred in July 2015. The median number of cycles of paclitaxel received was 4 (12 weeks). The median time on pazopanib was 11 weeks. Median overall survival was 8.0 months for paclitaxel [80% confidence interval (CI) 6.9 to 9.7 months] and 4.7 months for pazopanib [80% CI 4.2 to 6.4 months]. The hazard ratio (HR) adjusted for baseline stratification factors was 1.25 [80% CI 0.96 to 1.63; 1-sided p = 0.86] in favour of paclitaxel. Median progression free survival was 3.2 months for paclitaxel [80% CI 2.9 to 5.0 months] and 3.1 months for pazopanib [80% CI 2.7 to 3.8 months]. The adjusted HR for PFS was 1.06 [80% CI 0.83 to 1.36; 1-sided p = 0.62] (in favour of paclitaxel). Discontinuations for toxicity occurred in 6.3% and 20.0% for paclitaxel and pazopanib respectively. VHL, HIF1alpha, VEGFR2 and PD-L1 expression were measured from archived tissue and correlated with outcome. Conclusions: Pazopanib does not have greater efficacy than paclitaxel in the second line treatment of UBC. There is a trend towards superior OS with paclitaxel. Clinical trial information: NCT00949455.

Maintenance pazopanib versus placebo in Non-Small Cell Lung Cancer patients non-progressive after first line chemotherapy: A double blind randomised phase III study of the lung cancer group, EORTC 08092 (EudraCT: 2010-018566-23, NCT01208064)

BackgroundSwitch maintenance is an effective strategy in the treatment of advanced Non-Small Cell Lung Cancer (NSCLC). Pazopanib is an oral, multi-targeted tyrosine kinase inhibitor (TKI). EORTC 08092 evaluated pazopanib given as maintenance treatment following standard first line platinum-based chemotherapy in patients with advanced NSCLC. MethodsPatients with non-progressive disease after 4–6 cycles of chemotherapy were randomised to receive either pazopanib 800mg/day or matched placebo until progression or unacceptable toxicity. The primary end-point was overall survival and secondary end-points were progression-free survival (PFS) and safety. ResultsA total of 600 patients were planned to be randomised. The trial was prematurely stopped following an early interim analysis, after 102 patients were randomised to pazopanib (n=50) or placebo (n=52). Median age was 64years in both arms. Median overall survival was 17.4months for pazopanib and 12.3months for placebo (adjusted hazard ratio (HR) 0.72 [95% confidence interval (CI) 0.40–1.28]; p=0.257). Median PFS was 4.3months versus 3.2months (HR 0.67, [95% CI 0.43–1.03], p=0.068). PFS rates at 4months were 56% and 45% respectively. The majority of treatment-related adverse events (AEs) were grade 1–2. Grade 3–4 AEs (pazopanib versus placebo) were hypertension (38% versus 8%), neutropenia (8% versus 0%), and elevated SGPT (6% versus 0%). Of the patients randomised to pazopanib, 22% withdrew due to a treatment-related AE. ConclusionsSwitch maintenance with pazopanib following platinum-based chemotherapy in advanced NSCLC patients had limited side-effects. This study was stopped due to lack of efficacy by stringent criteria for PFS at a futility interim analysis.

Plasma cytokine and angiogenic factors (CAFs) predictive of clinical benefit and prognosis in patients (Pts) with advanced or metastatic renal cell cancer (mRCC) treated in phase III trials of pazopanib (PAZO).

334 Background: PAZO is a multikinase inhibitor approved for the treatment of mRCC. From phase II study of PAZO in mRCC (VEG102616), plasma CAF analysis from 3 different platforms (cross platform correlation r &gt;0.70) revealed several candidate CAFs including HGF, IL-6, IL-8, TIMP-1, VEGF, E-Selectin and OPN were found to be significantly correlated with clinical benefit (Tran ASCO 2010, #4522). To validate these findings, plasma were analyzed for CAFs from mRCC pts enrolled in phase III randomized, placebo controlled trial with PAZO where progression-free survival (PFS) of 9.2 months of PAZO and 4.2 months of placebo (hazard ratio:0.46 p&lt;.0001) and overall response rate 30% was observed (Sternberg, JCO, 2010). Methods: Plasma samples (n=344) from phase III randomized, placebo-controlled trial (VEG105192) were analyzed for candidate CAFs by a CLIA-certified laboratory (Aushon Biosystems, MA). These markers of PAZO and placebo arms were correlated with PFS by Cox regression and plotted in Kaplan Meier by using median concentration of each marker as a cutoff. Results: Higher levels of IL-8 (p&lt;0.006), HGF (p&lt;0.01), OPN (p&lt;0.001) and TIMP-1 (p&lt;0.006) were associated with shorter PFS in PAZO treated pts. Higher levels of all these markers except HGF were also associated with shorter PFS in the placebo arm (IL-8 (p&lt;0.002), OPN (p&lt;0.001), IL-6 (&lt;0.001), TIMP-1 borderline at p= 0.052) and were therefore prognostic. Only IL-6 was predictive of PFS benefit; pts with high IL-6 had a greater relative benefit from PAZO compared to placebo with a HR of 0.32 in the high IL-6 group and 0.57 in the low IL-6 group (p value for interaction 0.009). Conclusions: This study validated HGF, IL-8, OPN, and TIMP-1 as markers associated with clinical benefit with PAZO treatment. IL-8 and OPN were confirmed as prognostic markers in the placebo arm and IL-6 was both a prognostic marker and predictive marker for pazopanib therapy. [Table: see text]