Predictive value of primary tumor location (TL) in patients (pts) with pan-RAS wild-type (wt) metastatic colorectal cancer (mCRC) receiving chemotherapy (CTX) ± cetuximab or panitumumab (C/P): An updated meta-analysis.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 830-830 ◽  
Author(s):  
Zi-Xian Wang ◽  
Ming-ming He ◽  
Ying-Nan Wang ◽  
Feng Wang ◽  
Rui-hua Xu
Keyword(s):  
Random Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Randomized Controlled ◽  
Analytic Models

830 Background: Previous evidence suggests that TL may be predictive of the efficacy of C/P versus bevacizumab. This meta-analysis was aimed to evaluate the efficacy of CTX plus C/P versus CTX only as a first-line (1L) or second-line (2L) treatment for RAS wt right- and left-sided mCRC (R- and L-mCRC) in randomized controlled trials (RCTs). Methods: A systematic literature review was performed of PubMed and oncology congress websites (2000–present). RCTs studying the additional efficacy of C/P to CTX in RAS wt R- and L-mCRC were included. Assessed outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Random-effects meta-analytic models were used in the presence of significant heterogeneity ( I2> 50%). Otherwise, fixed-effects models were performed. Random-effects meta-regression models were used to evaluate the interaction between TL and the efficacy of C/P. Results: A total of three 1L RCTs (CRYSTAL, PRIME, and TAILOR) and one 2L RCT (20050181) were included (325 pts with R-mCRC and 1214 with L-mCRC). Pooled estimates of the efficacy of C/P are summarized in the table. In both R- and L-mCRC pts, the addition of C/P to CTX significantly improved PFS and ORR. A significant OS benefit from C/P was observed in L-mCRC but not R-mCRC pts. No significant interaction was detected between TL and the efficacy of C/P on PFS, OS, and ORR ( P= 0.69, 0.09, and 0.22, respectively). Conclusions: Adding C/P to CTX clearly benefits RAS wt L-mCRC pts in terms of PFS, OS, and ORR. Considering the improvements in PFS and ORR versus CTX only, anti-EGFR agents remain an option for pts with RAS wt R-mCRC. [Table: see text]

scholarly journals FOLFOXIRI versus FOLFOX or FOLFIRI with targeted therapy in patients with mutant BRAF metastatic colorectal cancer: A systematic review and meta-analysis

2020 ◽  
pp. 125-132
Author(s):  
M. Yu. Fedyanin ◽  
E. M. Polyanskaya ◽  
H. H.-M. Elsnukaeva ◽  
A. A. Tryakin ◽  
I. A. Pokataev ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Metastatic Colorectal Cancer ◽  
Subgroup Analysis ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Systemic Review ◽  
Free Survival

Introduction. Based on the subgroup analysis of the TRIBE study FOLFOXIRI with bevacizumab is the recommended option for patients (pts) with mBRAF metastatic colorectal cancer (mCRC) in the 1st line. However, subgroup analysis of other studies showed conflicting results. Therefore, we performed systemic review and meta-analysis to compare efficacy FOLFOXIRI and doublets with targeted therapy in pts with mBRAF mCRC in terms of progression free survival (PFS), objective response rate (ORR) and overall survival (OS).Methods. We performed a search of all prospective randomizes studies in PubMed, ASCO and ESMO congresses for all years before May, 2020, compared FOLFOXIRI plus bevacizumab or anti-EGFR antibodies and FOLFOX or FOLFIRI with targeted agents at the 1st line with information of the BRAF status. Primary outcome was hazard ratio (HR) for PFS and 95% confidence interval (CI); secondary – HR for OS and odds ratio (OD) for ORR. Fixed effects were used for analysis. Meta-analysis was conducted by Review Manager Ver. 5.3.Results. We identified 6 trials (CHARTA, STEAM, TRIBE, TRIBE2, VISNU, METHEP2), which included 158 pts with mBRAF (FOLFOXIRI – 82 (52%) and doublets – 76 (48%). According to results of the meta-analysis there was a tendency for higher ORR in pts with FOLFOXIRI (OR 2.07, 95% CI 0.61–7.06; p = 0.24; I2 = 27%, p for heterogeneity 0.26; 3 trials). However we didn’t find any significant improvement in PFS (HR 0.89, 95% CI 0.64–1.23; p = 0.48; I2 = 0%, p for heterogeneity 0.63; 5 trials) or OS (HR 0.9, 95% CI 0.37–1.19; p = 0.048; I2 = 71%, p for heterogeneity 0.06; 2 trials) in the group of triplet.Conclusions. FOLFOXIRI with targeted therapy did not show significant improvement in the PFS and OS in pts with mBRAF compared with FOLFOX or FOLFIRI with targeted antibodies. A prospective randomized trial is needed to determine the optimal chemotherapy regimen at the 1st line for pts with mBRAF mCRC.

scholarly journals The relationship between time to surgery after neoadjuvant chemotherapy and survival in breast cancer patients:a meta-analysis

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Random Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Fixed Effects Model ◽  
Free Survival ◽  
The Impact ◽  
The Relationship

Abstract PURPOSE: This meta-analysis aims to evaluate the impact of delaying surgery in operable breast tumor patients after neoadjuvant chemotherapy (NAC) on survival. METHODS:An electronic literature retrieval was conducted on PubMed/Medline and EMBASE((between January 2000 and June 2020).The primary end point was overall survival(OS),secondary end points included disease-free survival (DFS) or recurence-free survival (RFS).The HR with 95% confidence intervals were calculated using a random-effects or fixed-effects model. RESULTS:The combined HR for OS was 1.51 (95% CI:1.30-1.76; P=0.000) by fixed effects model.No statistically significant heterogeneity was found (P=0.168, I 2 =31.3%).The pooled HR for RFS/DFS was 1.59 (95%CI:1.30-1.95,I 2 = 66.0%) by random-effects model,with significant heterogeneity. CONCLUSION:Our meta-analysis revealed a significant adverse association between longer TTS after NAC and more inferior OS and RFS/DFS in patients with breast cancer.Clinicians and patients should minimize surgical delay after NAC as much as possible.

scholarly journals A Systematic Review and Network Meta-Analysis of Randomized Data on Efficacy of Novel Therapy Combinations in Patients with Lenalidomide Refractory Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-12
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Jill Hampton ◽  
Muhammad Aziz ◽  
Sadik Khuder ◽  
Saad Ullah Malik ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Treatment Regimens ◽  
Randomized Controlled

Introduction: Advancements in the treatment of multiple myeloma (MM) with proteasome inhibitors [bortezomib (bort), carfilzomib (carf)], monoclonal antibodies [daratumumab (dara), isatuximab (isa) and elotozumab (elo)], and immunomodulatory drugs [IMiD) [lenalidomide and pomalidomide (pom)] have improved outcomes. However, using lenalidomide as frontline treatment and maintenance therapy exposes greater numbers of patients to lenalidomide prior to relapse. Consequently, the treatment of lenalidomide-refractory (LR) disease is an increasing area of concern. Given the lack of direct comparisons of different treatment regimens for LR MM, we used a systematic review to identify randomized controlled trials (RCTs) that included subgroup analysis of LR patients. The objective of our study was to compare the efficacy of novel treatment regimens in randomized trials for patients with LR MM using a network meta-analysis. Methods: Three databases were searched: MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials. All studies published between January 1, 2005 and December 30, 2019 were queried using keywords "multiple myeloma" and "randomized controlled trial". Only RCT's were included. Primary outcome was progression free survival (PFS) of patients enrolled in myeloma RCT's. Two independent investigators reviewed all the studies and resolved any conflict through mutual discussion. WNetwork meta-analysis using random-effects model was performed to generate direct and indirect comparisons between various treatment groups. Frequentist method was used to rank the interventions and P-score was generated. A higher P score (close to 1.00) corresponded to superior progression free survival. A P-value of <0.05 was considered statistically significant. Hazard ratios (HR) with 95% confidence interval (CI) were calculated. I2statistic was used to assess heterogeneity between the studies as defined by the Cochrane Handbook for Systematic Reviews with a value >50% considered as significant heterogeneity. We used 'R' (Bell Labs, Murray Hill, NJ, USA) for generating our statistical analysis and plots. Results: Our initial search strategy yielded 1171 results. After excluding duplicates, trials in progress, subset analysis and non-randomized studies, 123 RCTs were identified. Only 8 studies clearly reported outcomes of patients with LR myeloma and 7 studies (1698 patients) were included in final analysis of two discrete networks. Pom/bort/dex (HR: 0.65,95% CI: 0.50-0.84), dara/bort/dex (HR: 0.36, 95% CI: 0.21-0.63), and dara/carf/dex (HR: 0.38, 95% CI: 0.21-0.69) were all found to have improved PFS compared to bort/dex (Figure 2). These interventions were ranked as follows: Dara-bort-dex was the most efficacious with a P-score of 0.8758, followed by Dara/carf/Dex (P of 0.8514), Pom/bort/dex (P of 0.4791), Carf/dex (P of 0.2707) and Bort/dex (P of 0.0231). Within Network 2 (Figure 3), pom/dex (HR :0.50, 95% CI= 0.40-0.62), isa/pom/dex (HR: 0.30, 95% CI= 0.20-0.44) and elo/pom/dex (HR: 0.27, 95% CI=0.16-0.45), were all found to have improved PFS compared to dexamethasone (Figure 4). In Network 2, the ranking of interventions was as follows with Elo-pom-dex (P of 0.8716) the most efficacious, followed by Isa-pom-Dex (P of 0.7932) and Pom-dex (P of 0.3352). Conclusion: The results of our network meta-analysis of 1698 patients with lenalidomide refractory myeloma enrolled in seven randomized myeloma trials demonstrate that for lenalidomide refractory myeloma, triplet therapy is superior to doublet therapy. Regimens with the highest efficacy in this subset of patients were triplets containing monoclonal antibodies (such as dara/elo/isa). There is a need for further randomized data to better ascertain the best standard of care for these patients. Disclosures No relevant conflicts of interest to declare.

The relationship between time to surgery(TTS) after neoadjuvant chemotherapy (NAC)and survival in breast cancer patients: meta-analysis

2020 ◽  
Author(s):  
YongCheng Su ◽  
XiaoGang Zheng
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Random Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
The Impact ◽  
The Relationship

Abstract PURPOSE: This meta-analysis aims to evaluate the impact of delaying surgery in operable breast tumor patients after neoadjuvant chemotherapy (NAC) on survival.METHODS: An electronic literature retrieval was conducted on PubMed/Medline and EMBASE((between January 2000 and June 2020).The primary end point was overall survival(OS),secondary end points included disease-free survival (DFS) or recurrence-free survival (RFS).The HR with 95% confidence intervals were calculated using a random-effects or fixed-effects model.RESULTS: The combined HR for OS was 1.52(95% CI 1.29-1.78; P = 0.000) by fixed-effects model.No statistically significant heterogeneity was found (P=0.114;I2=39.8%).The pooled HR for RFS/DFS was 1.47 (95%CI: 1.27- 1.71,I2=61.9%) by random-effects model, with significant heterogeneity.CONCLUSION: Our meta-analysis revealed a significant adverse association between longer TTS after NAC and more inferior OS and RFS/DFS in patients with breast cancer.Clinicians and patients should minimize surgical delay after NAC as much as possible.

scholarly journals The Efficacy of Ramucirumab in the Treatment of Gastric or Gastroesophageal Junction Cancer: A Meta-Analysis of RCTs

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Hongqiong Yang ◽  
Yaojun Zhou ◽  
Liangzhi Wang ◽  
Tianyi Gu ◽  
Mengjia Lv ◽  
...  
Keyword(s):  
Response Rate ◽  
Meta Analysis ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
First Line ◽  
Free Survival ◽  
Gastroesophageal Junction Cancer ◽  
Line Chemotherapy

Five electronic databases were searched for eligible records. Outcomes were presented and analyzed according to the objective response rate (ORR), progression-free survival (PFS) rate, and overall survival (OS) rate. Five records involving 2,024 participants were included in the study. The pooled analysis of OS and PFS were longer with ramucirumab (RAM) therapy than without RAM for OS (odds ratio OR = 0.90 , 95% confidence interval CI = 0.82 – 1.00 , p = 0.05 ) and PFS ( OR = 0.74 , 95 % CI = 0.57 – 0.96 , p = 0.02 ). Moreover, compared with the current first-line chemotherapy, the OS ( OR = 0.93 , 95 % CI = 0.83 – 1.04 , p = 0.19 ) and PFS ( OR = 0.82 , 95 % CI = 0.64 – 1.06 , p = 0.13 ) results were not significantly higher with RAM. The ORRs of the patients in the RAM therapy groups were significantly higher than those in the groups without RAM ( OR = 1.40 , 95 % CI = 1.14 – 1.73 , p = 0.001 ).

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Clinical Equipoise for Trials of Novel Biologic Therapies, Therapeutic Success Rates, and Predictors of Success: A Meta-Analysis

2017 ◽  
pp. 1-12
Author(s):  
Doah Cho ◽  
Felicia T. Roncolato ◽  
Johnathan Man ◽  
John Simes ◽  
Sarah J. Lord ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
Predictors Of Success ◽  
Biologic Therapies ◽  
Therapeutic Success ◽  
Free Survival ◽  
Randomized Controlled ◽  
Phase Iii Trials

Purpose The demand for more rapid access to novel biologic therapies than randomized controlled trials can deliver is a topic of ongoing study and debate. We aimed to inform this debate by estimating therapeutic success from phase III trials comparing novel biologic therapies with standard of care and identifying predictors of success. Methods This was a meta-analysis of phase III trials evaluating novel biologic therapies in advanced breast, colorectal, lung, and prostate cancers. Therapeutic success was defined as statistically significant results for the primary end point favoring novel biologic therapies. Results Of 119 included phase III trials (76,726 patients), therapeutic success was 41%, with a statistically significant relative reduction in disease progression and death for novel biologic therapies over standard of care of 20% and 8%. Therapeutic success did not improve over time (pre-2010, 33%; 2010 to 2014, 44%; P = .2). Predictors of success were a biomarker-selected population (odds ratio, 4.74; 95% CI, 2.05 to 10.95) and progression-free survival end point compared with overall survival (odds ratio, 5.22; 95% CI, 2.41 to 11.39). Phase III trials with a biomarker-selected population showed a larger 28% progression-free survival benefit than phase III trials overall (hazard ratio, 0.72; 95% CI, 0.70 to 0.75) but similar 8% overall survival benefit (hazard ratio, 0.92; 95% CI, 0.90 to 0.94). Therapeutic success of phase III trials with and without a preceding phase II trial were 43% and 30%, respectively Conclusion Therapeutic success of novel biologic therapies in phase III trials, including therapies with a matching predictive biomarker, was modest and has not significantly improved over time. Equipoise remains and supports the ongoing ethical and scientific requirement for phase III randomized controlled trials to estimate treatment efficacy and assess the value of potential biomarkers.

scholarly journals Prognostic Role of Matrix Metalloproteinases in Cervical Cancer: A Meta-Analysis

2021 ◽  
Vol 28 ◽  
pp. 107327482110337
Author(s):  
Weiwei Chen ◽  
Shenjiao Huang ◽  
Kun Shi ◽  
Lisha Yi ◽  
Yaqiong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Matrix Metalloproteinases ◽  
Random Effects ◽  
Fixed Effects ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Free Survival ◽  
Random Effects Models ◽  
Registration Number ◽  
Meta Analyses

Objective Studies have published the association between the expression of matrix metalloproteinases (MMPs) and the outcome of cervical cancer. However, the prognostic value in cervical cancer remains controversial. This meta-analysis was conducted to evaluate the prognostic functions of MMP expression in cervical cancer. Methods A comprehensive search of PubMed, Embase, and Web of Science databases was conducted to identify the eligible studies according to defined selection and excluding criteria and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Fixed and random effects models were evaluated through the hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the overall survival (OS), recurrence-free survival (RFS), and progress-free survival (PFS). Results A total of 18 eligible studies including 1967 patients were analyzed for prognostic value. Totally 16 selected studies including 21 tests were relevant to the cervical cancer OS, 4 studies focused on RFS, and 1 study on PFS. The combined pooled HRs and 95% CIs of OS were calculated with random-effects models (HR = 1.64, 95% CI = 1.01–2.65, P = .000). In the subgroup analysis for OS, there was no heterogeneity in MMP-2 (I2 = .0%, P = .880), MMP-1 (I2 = .0%, P = .587), and MMP-14 (I2 = 28.3%, P = .248). In MMP-7 and MMP-9, the heterogeneities were obvious (I2 = 99.2% ( P = .000) and I2 = 77.9% ( P = .000), respectively). The pooled HRs and 95% CIs of RFS were calculated with fixed-effects models (HR = 2.22, 95% CI = 1.38–3.58, P = .001) and PFS (HR = 2.29, 95% CI = 1.14–4.58, P = .035). Conclusions The results indicated that MMP overexpression was associated with shorter OS and RFS in cervical cancer patients. It suggested that MMP overexpression might be a poor prognostic marker in cervical cancer. Research Registry Registration Number: reviewregistry 1159.

scholarly journals Systematic review and meta-analysis of docetaxel perioperative chemotherapy regimens in gastric and esophagogastric tumors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pedro Luiz Serrano Uson Junior ◽  
Vanessa Montes Santos ◽  
Diogo Diniz Gomes Bugano ◽  
Elivane da Silva Victor ◽  
Edna Terezinha Rother ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Significant Heterogeneity ◽  
Free Survival ◽  
Dose Ranging ◽  
Prospective Trials ◽  
Grade 3 ◽  
One Year

Abstract FLOT regimen became the standard perioperative treatment in several centers around the world for esophagogastric tumors despite concerns about toxicity. In addition, FLOT has never been compared with other docetaxel-based regimens. To address this question, we conducted a systematic review of PubMed, Embase and Web of Science including prospective or retrospective studies of docetaxel based perioperative regimen in gastric and esophagogastric tumors. Data regarding chemotherapy regimens, efficacy and toxicity were extracted. Outcomes were compared using a random effects model. Of 548 abstracts, 16 were considered eligible. Comparing the studies with meta-analysis we can see that the regimens are similar in terms of pathological complete response, resection rate, progression free survival and overall survival in one year, without significant heterogeneity. The meta-regression of docetaxel dose failed to show any association with dose ranging between 120–450 mg/m². Regarding the toxicity of the regimens it is noted that the regimens are quite toxic (up to 50–70% of grade 3–4 neutropenia). The results of this meta-analysis with a combined sample size of more than 1,000 patients suggest that docetaxel perioperative regimens are equivalent in outcomes. Prospective trials addressing modified regimens should be performed to provide less toxic strategies and be applicable to all patients.

Sign in / Sign up

Export Citation Format

Share Document