Showing papers by "Sylvie Negrier published in 2009"
TL;DR: Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC, highlighting an improved prognosis in patients with RCC in the era of targeted therapy.
Abstract: Purpose A randomized, phase III trial demonstrated superiority of sunitinib over interferon alfa (IFN-α) in progression-free survival (primary end point) as first-line treatment for metastatic renal cell carcinoma (RCC). Final survival analyses and updated results are reported. Patients and Methods Seven hundred fifty treatment-naive patients with metastatic clear cell RCC were randomly assigned to sunitinib 50 mg orally once daily on a 4 weeks on, 2 weeks off dosing schedule or to IFN-α 9 MU subcutaneously thrice weekly. Overall survival was compared by two-sided log-rank and Wilcoxon tests. Progression-free survival, response, and safety end points were assessed with updated follow-up. Results Median overall survival was greater in the sunitinib group than in the IFN-α group (26.4 v 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% CI, 0.673 to 1.001; P = .051) per the primary analysis of unstratified log-rank test (P = .013 per unstratified Wilcoxon test). By stratified log-rank test, the HR wa...
2,015 citations
TL;DR: Although an OS benefit was not seen on a primary intent-to-treat analysis, results of a secondary OS analysis censoring placebo patients demonstrated a survival advantage for those receiving sorafenib, suggesting an important cross-over effect.
Abstract: Purpose Mature survival data and evaluation of vascular endothelial growth factor (VEGF) as a prognostic biomarker from the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) study in patients with renal cell carcinoma (RCC) are reported. Patients and Methods Nine hundred three previously treated patients were randomly assigned to receive sorafenib versus placebo. On demonstration of progression-free survival (PFS) benefit with sorafenib, patients assigned to placebo were offered sorafenib. Overall survival (OS) was determined at two planned interim analyses and one final analysis, with a secondary OS analysis conducted by censoring placebo patients who crossed over to sorafenib. The relationships between baseline VEGF level and prognosis and efficacy were evaluated. Results The final OS of patients receiving sorafenib was comparable with that of patients receiving placebo (17.8 v 15.2 months, respectively; hazard ratio [HR] = 0.88; P = .146); however, when post–cross-over placebo survi...
1,049 citations
TL;DR: Sorafenib resulted in similar PFS as IFN-alpha-2a in patients with untreated RCC, however, sorafenIB-treated patients experienced greater rates of tumor size reduction, better QOL, and improved tolerability.
Abstract: Purpose An open-label, phase II study to evaluate progression-free survival (PFS), overall best response, adverse events (AEs), and patient-reported outcomes with sorafenib versus interferon alfa-2a (IFN-α-2a) in patients with untreated, advanced renal cancer. Patients and Methods A total of 189 patients were randomly assigned to oral sorafenib 400 mg twice daily or to subcutaneous IFN-α-2a 9 million U three times weekly (period 1). Sorafenib patients who progressed were dose-escalated to 600 mg twice daily; IFN-α-2a patients who progressed were switched to sorafenib 400 mg twice daily (period 2). Results In period 1 PFS was similar for sorafenib-treated (n = 97; 5.7 months) and IFN-α-2a–treated patients (n = 92; 5.6 months); more sorafenib-treated patients had tumor shrinkage (68.2% v 39.0%). Common drug-related AEs (Grades ≥ 3) for sorafenib were hand-foot skin reaction (11.3%), diarrhea (6.2%), and rash/desquamation (6.2%); for IFN-α-2a, these were fatigue (10.0%), nausea (3.3%), flu-like syndrome (2.2...
453 citations
TL;DR: Overall this retrospective study supports the conclusion of the lack of absolute cross-resistance between tyrosine kinase inhibitors between renal cell carcinoma patients.
153 citations
TL;DR: BEV + IFN is a first-line standard of care for pts with mRCC, improving PFS and ORR, with a trend toward improved OS, compared with IFN.
Abstract: 5020 Background: In the AVOREN trial, BEV (Avastin) + IFN significantly improved PFS and ORR compared with placebo + IFN in pts with mRCC [Escudier, Lancet. 2007]. The study was unblinded after int...
88 citations
TL;DR: It is suggested that the progression-free and overall survival benefits seen in mRCC patients aged 65 years and over are similar to those in the younger age group, and the frequency of major toxicities in elderly patients treated with targeted agents is no greater than in younger patients.
Abstract: Treatments currently recommended for metastatic renal cell cancer (mRCC) have not been evaluated specifically in elderly patients. Here we consider what may be learned by analysing according to age the efficacy and toxicity data from key phase III trials of the targeted agents sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel), and bevacizumab (Avastin), and from a study of expanded access to sunitinib and sorafenib. This paper represents the first systematic review of the role of targeted agents specifically in the elderly population. Retrospective subgroup analyses of clinical trial data cannot be considered definitive. However, they suggest in general that the progression-free and overall survival benefits seen in mRCC patients aged 65 years and over are similar to those in the younger age group. The frequency of major toxicities in elderly patients treated with targeted agents is no greater than in younger patients, although such toxicities may have greater impact on the quality of life. That said, no meaningful data are available for patients over 85 years. To confirm and extend these conclusions, prospective studies should be undertaken in the elderly to determine whether recommendations made for the wider mRCC population apply equally to this group of patients in whom comorbidities, comedication and the greater impact of low-grade toxicity may influence the efficacy and tolerability of treatment. Such studies are increasingly needed, given the growing number of elderly people and their rising life expectancy. Meanwhile, when considering the most appropriate drug to use in a particular patient, the toxicity profiles of the individual targeted agents--and any implications for specific comorbid conditions--should be taken into account.
87 citations
TL;DR: Multivariate analysis of sunitinib patients found factors associated with longer OS include: interval from diagnosis to treatment ≥1 yr, ECOG PS of 0, lower corrected calcium, absence of bone metastases, lower lactic dehydrogenase (LDH), and higher hemoglobin (Hgb) ( table ).
Abstract: 5042 Background: Sunitinib demonstrated superior progression-free survival (PFS; the primary endpoint) over interferon-alfa (IFN-α) as first-line mRCC therapy (NEJM 2007;356:115). Median overall survival (OS) with sunitinib compared to IFN-α was: 26.4 vs. 21.8 months (HR=0.821; P=0.051 by unstratified log-rank test; Proc ASCO 2008;26, May 20 suppl; abstr 5024). An analysis of prognostic factors for OS was performed on data from this trial. Methods: 750 treatment-naive mRCC patients were randomized 1:1 to receive sunitinib or IFN-α. By Cox proportional hazards model, selected pretreatment variables were evaluated univariately and in a multivariate model for each treatment arm. Multivariate models for each treatment arm were based on a stepwise algorithm with a type I error of 0.25 for entry and 0.15 for elimination. Further elimination was applied to identify variables significant at P<0.05. Results: In multivariate analysis of sunitinib patients, factors associated with longer OS include: interval from di...
17 citations
SIDI1
TL;DR: There is no major difference of efficacy and safety between cetuximab given every 2 weeks and a weekly dosing regimen, in association with irinotecan in patients with metastatic colorectal cancer (MCRC).
Abstract: Aim : The aim of the present study was to compare the efficacy and safety of weekly versus an every 2-week administration of cetuximab in association with irinotecan in patients with metastatic colorectal cancer (MCRC). Methods : We reviewed the clinical records of 50 patients with MCRC who began treatment with cetuximab from February 2004 to January 2007. Two different treatment schedules were used. In the first group (N = 32), cetuximab was given at an initial dose of 400 mg/m 2 , followed by weekly infusions of 250 mg/m 2 . In the second group (N = 18), cetuximab was administered every 2 weeks at a dose of 500 mg/m 2 . The two groups were compared for tumor response, time to progression (TTP), overall survival (OS), and toxicity. Results : All patients had received irinotecan and 5-fluorouracil; a majority had previously received oxaliplatin. Disease control (partial response + stable disease) was achieved in 56.3% of patients receiving weekly cetuximab versus 77.8% in the other group (P = 0.21). The median follow-up for all patients was 34.2 months. TTP (Group 1: 28% vs. Group 2: 18%, P = 0.9356) and OS (Group 1: 75% vs. Group 2: 72%, P = 0.6748) rates at 7 months were similar in the two groups. Skin toxicity was the most relevant adverse event: 78.1% of the patients had acne-like rash in the first group and 61% in the second group. However, only one patient in each group had a grade 3 toxic reaction. Conclusion : There is no major difference of efficacy and safety between cetuximab given every 2 weeks and a weekly dosing regimen, in association with irinotecan.
14 citations
TL;DR: A score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy.
Abstract: Background
We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients.
Methods
Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4).
Results
The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5×the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0–1], 2 and [3]–[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values.
Conclusions
We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy.
13 citations
10 citations
TL;DR: In this article, the most prevalent kidney cancer, RCC, is a relatively rare malignancy that carries a poor prognosis and new targeted therapies, such as sunitinib, sorafenib, temsirolimus, and beva...
Abstract: e17556 Background: RCC, the most prevalent kidney cancer, is a relatively rare malignancy that carries a poor prognosis. New targeted therapies, such as sunitinib, sorafenib, temsirolimus, and beva...