scholarly journals Bevacizumab-based first-line chemotherapy in elderly patients with metastatic colorectal cancer: an individual patient data based meta-analysis

Oncotarget ◽  
2017 ◽  
Vol 9 (12) ◽  
pp. 10272-10283 ◽  
Author(s):  
Christine Koch ◽  
Anna M. Schwing ◽  
Eva Herrmann ◽  
Markus Borner ◽  
Eduardo Diaz-Rubio ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
First Line ◽  
Line Chemotherapy

Treatment breaks in first line treatment of advanced colorectal cancer: an individual patient data meta-analysis

2021 ◽  
pp. 102226
Author(s):  
Richard Adams ◽  
Kaitlyn Goey ◽  
Benoist Chibaudel ◽  
Miriam Koopman ◽  
Cornelis Punt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Patient Data ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

First-Line Treatment and Outcome of Elderly Patients with Primary Central Nervous System Lymphoma (PCNSL) – A Systematic Review and Individual Patient Data Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3655-3655 ◽  
Author(s):  
Benjamin Kasenda ◽  
Andrés J.M. Ferreri ◽  
Emerenziana Maturano ◽  
Jacoline J.E.C. Bromberg ◽  
Herve Ghesquieres ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Central Nervous System Lymphoma ◽  
Patient Data ◽  
First Line ◽  
Eligibility Criteria ◽  
First Line Therapy ◽  
Line Therapy

Abstract Abstract 3655 Background Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma with devastating prognosis. High-dose methotrexate (HD-MTX) in combination with HD-cytarabine builds the backbone of current treatments. Elderly patients constitute 45% of cases, exhibit poor outcome and frequent iatrogenic toxicity. However, research efforts to optimize therapy in this subgroup have been neglected. On this background, we conducted a systematic review (SR) and individual patient data meta-analysis (IPDMA) to provide comprehensive evidence-based management strategy for elderly patients with PCNSL. Patients and Methods SR: We searched MEDLINE and EMBASE without language restriction. Eligibility criteria were prospective/retrospective observational studies or randomized trials (RCT) (all N>=10) that exclusively focused on first-line therapy/outcomes in immunocompetent PCNSL patients ≥60 years. Eligible studies were evaluated for methodological quality and reporting of the following baseline characteristics: Age, performance status (PS), involvement of deep brain structures (IDB), serum LDH at baseline, cerebro-spinal fluid (CSF) protein concentration elevation, neurotoxicity (as reported), specific co-morbidity indices, and functional status. For the IPDMA, investigators of eligible studies were asked to provide individual patient data. Minimal eligibility criteria: Age at baseline, details about first-line therapy, and follow-up information. If no data were available, studies were included in the SR, but not in the IPDMA. To maximize statistical power and generalizability, published/unpublished data from other international collaborators were included. Impact of different first-line treatments on overall survival (OS) was investigated using time dependent mixed effects multivariable Cox regression models (age and PS as fixed effects, study/database as random effect). Results SR: We identified 13 eligible studies including 583 patients in total, median age 68–76, published from 1996–2011. Design of studies: prospective (3 multicenter [1 RCT]; 2 single center), retrospective (4 multicenter and single-center, respectively). Accrual of the RCT was recently finished, but publication is pending. From published studies, information about age and therapy was given throughout, for clinical performance in 77%, for LDH and CSF protein in 15%, and IDB in 38%. Functional status was reported in only one study. From the identified 13 studies, 261 individual patient data were available for our IPDMA and pooled with 408 patients from other databases; altogether 669 patients diagnosed from 1977–2011. Preliminary results IPDMA: 50% were male, median age 68 (60–70 [N=431], 70–80 [N=211], >80 [N=22]); median KPS was 60% (10–100%). Therapy regimens widely varied. Overall response to first-line treatment was 65% (45% CR, 19% PR). After a median follow-up of 23 months (1–171), 44% were still alive, with a 3-year OS of 32% [95%CI, 29–37%]. Grouping by time of diagnosis revealed improvement for patients diagnosed after 1997 (N=462) (P<0.001). In multivariate analysis, MTX-based poly-chemotherapy (CT) (N=474) was associated with improved OS (Hazard ratio [HR] 0.69, 95% CI 0.52–0.91) compared to non-MTX regimens (N=195); this was consistent among patients who received consolidating WBRT (HR 0.33, 95% CI 0.01–0.66) and those who did not (HR 0.46, 95% CI 0.23–0.89). In patients who received any MTX-based poly-CT, addition of CHOP-like components (N=90) was not associated with improved OS (HR 0.98, 95% 0.65–1.48). Although any WBRT showed an overall trend for superior OS, it was associated with a 4-fold risk increase for neurotoxicity (Odds Ratio 4.21, 95% CI 2.23–8.21). Further results of treatment patterns and explorative comparisons will be presented at the meeting. Conclusion This international meta-analysis revealed widely varying treatment approaches and demonstrates that prognosis for elderly PCNSL patients is still poor. However, improvement over the last decades was observed. MTX-based poly-CT was associated with better outcome compared to non-MTX containing approaches. The addition of CHOP-like regimens to HD-MTX did not improve outcome. WBRT was associated with better outcome, but also clearly increased risk of neurotoxicity. Prospective trials designed ad hoc for elderly PCNSL patients are promptly needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

2015 ◽  
Vol 33 (1) ◽  
pp. 22-28 ◽  
Author(s):  
Qian Shi ◽  
Aimery de Gramont ◽  
Axel Grothey ◽  
John Zalcberg ◽  
Benoist Chibaudel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Individual Patient Data ◽  
Progression Free Survival ◽  
Patient Data ◽  
Biologic Agents ◽  
First Line ◽  
Free Survival ◽  
End Point

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents.

Th17 cell pathway-related genetic variants in metastatic colorectal cancer: A meta-analysis using TRIBE, MAVERICC, and FIRE-3.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 594-594
Author(s):  
Ryuma Tokunaga ◽  
Shu Cao ◽  
Francesca Battaglin ◽  
Jae Ho Lo ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Meta Analysis ◽  
Candidate Snps ◽  
First Line ◽  
Q Statistic ◽  
Line Chemotherapy

594 Background: Th17 cells constitute a subset of T-helper cells, and play a role in immune response to extracellular pathogens in the human intestinal tract. Further, Th17 cells are associated with tumor angiogenesis and enhanced efficacy of 5-FU treatment. We thus investigated associations between the Th17 cell pathway-related SNPs and clinical outcomes in patients with metastatic colorectal cancer (mCRC) treated with conventional chemotherapy. Methods: We analyzed a total of 884 patients with mCRC enrolled in three randomized clinical trials (TRIBE, MAVERICC, and FIRE-3: where patients were treated with FOLFIRI, mFOLFOX6, or FOLFOXIRI combined with bevacizumab or cetuximab as the first-line chemotherapy). Multivariable logistic regression and Cox regression were performed to evaluate the association between candidate SNPs in the Th17 cell pathway and clinical outcomes [tumor response (TR), progression-free survival (PFS), and overall survival (OS)] in each treatment cohort. The meta-analysis approach using the METASOFT software were implemented to quantify the prognostic effect of each SNP using the inverse-variance-weighted effect size, and also to evaluate the heterogeneity across cohorts using the Q statistic. SNPs were coded as additive, dominant, or recessive in the analysis. The Pegasus analysis was also used to identify effects across multiple SNPs and treatment arms. Results: Pathway analysis showed that the Th17 cell pathway was significantly associated with TR ( P = 0.011). There were suggestive associations of IL17F rs763780 with TR (log OR = 0.64, SE = 0.31; P = 0.038), of IL23R rs10889677 with TR (log OR = 0.37, SE = 0.18; P = 0.039), of IRF4 rs872071 with TR (log OR = -0.26, SE = 0.13; P = 0.037), and of IL21 rs2221903 with PFS (log HR = 0.33, SE = 0.15; P = 0.026), although these results were not significant after FDR adjustment. In addition, IL23R rs10889677 had suggestive heterogeneity of effects for PFS across the six cohorts after Cochran’s Q statistic ( P = 0.013). Conclusions: Th17 cell pathway-related SNPs may be predictors for the first-line chemotherapy in mCRC. Upon validation, our findings would provide novel insight for selecting treatment strategies for mCRC.

Impact of the addition of bevacizumab, oxaliplatin or irinotecan to fluoropyrimidin in the first-line treatment of metastatic colorectal cancer in elderly patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15034-e15034
Author(s):  
Thierry Landre ◽  
Thomas Aparicio ◽  
Djamel Ghebriou ◽  
Patrick Nicolas ◽  
Cherifa Taleb ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Front Line ◽  
First Line ◽  
Free Survival ◽  
Hazard Ratios ◽  
Selection Of

e15034 Background: The clinical benefit of double-front-line therapy (including oxaliplatin or irinotecan or bevacizumab plus 5FU or capecitabine) compared to monotherapy (5FU or capecitabine) in elderly ( > 70 years) patients with metastatic colorectal cancer (MCRC) is controversial. We performed a meta-analysis of published randomized studies. Methods: The selection of the studies was carried out using PubMed with the following keywords: "metastatic colorectal cancer", "elderly", "oxaliplatin", "irinotecan", "bevacizumab", "survival". The efficacy endpoints were overall survival (OS) and progression-free survival (PFS). Hazard Ratios (HRs) with their 95% confidence intervals (CIs) were collected from the studies and pooled. By convention, a HR < 1 was a result in favor of bitherapy. Results: This meta-analysis (MA) included nine studies: three assess irinotecan (FFCD 2001-02, CAIRO and an already published MA); three others assess oxaliplatin (FOCUS2, FFCD 2000-05 and FOLFOX pivotal trial) and the last three ones assess bevacizumab (AVEX, AGITG-MAX and AVF2192g). Our MA included 1600 patients (62% of men). Concerning age, we chose a cut-off of 70 years or a cut-off of 75 years, corresponding to the available data for each study. The performance index (PS) was 0-1 for about 90% of patients, with the exception of FFCD 2001-02 and FOCUS2 which included 30% of patients with PS2. Overall, the addition of bevacizumab to fluoropyrimidin statistically improved both OS and PFS (HR = 0.78; CI: 0.62–0.98 and HR = 0.51; CI: 0.41–0.64, respectively). The addition of oxaliplatin statistically improved PFS (HR = 0.81; CI: 0.67–0.97) but not OS (HR = 0.99; CI: 0.85–1.17) as well as the addition of irinotecan (HR = 0.83; CI: 0.68–1.00 and HR = 1.01; CI: 0.84–1.22, respectively). Conclusions: In previously untreated elderly patients with MCRC, the addition of bevacizumab to fluoropyrimidin appears more effective in terms of OS or PFS than the addition of oxaliplatin or irinotecan.

Sign in / Sign up

Export Citation Format

Share Document