scholarly journals Network Meta-Analysis of Efficacy and Safety of Chemotherapy and Target Therapy in the First-Line Setting of Advanced Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1746 ◽  
Author(s):  
Kun-I Lin ◽  
Jia-Lian Yang ◽  
Yu-Chao Lin ◽  
Che-Yi Chou ◽  
Jin-Hua Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Current Evidence ◽  
P Value ◽  
Efficacy And Safety ◽  
First Line ◽  
Free Survival

Both gemcitabine and fluoropyrimidine are recommended backbones in the first-line treatment of pancreatic ductal adenocarcinoma (PDAC). To compare the efficacy and safety of these two therapeutic backbones, and to investigate the optimal therapies, we conducted a network meta-analysis. By retrospective analysis of randomized controlled trials (RCT), the most preferred therapeutic regimen may be predicted. The eligible RCTs of the gemcitabine-based therapies and fluoropyrimidine-based therapies were searched up to 31 August 2019. In a frequentist network meta-analysis, treatments were compared and ranked according to overall survival (OS) and progression-free survival (PFS). Thirty-two trials with 10,729 patients were included. The network meta-analyses results for overall survival and progression-free survival showed that fluoropyrimidine-based therapy seems to be the most effective treatment choice. Compared to gemcitabine combined with taxanes or immunotherapy, fluoropyrimidine-based therapy had comparable treatment effects (PFS: 0.67, p-Value = 0.11; 0.76, p-Value = 0.32; OS: 0.80, p-Value = 0.16; 0.77, p-Value = 0.21). Moreover, the combination of immunotherapy and gemcitabine had tolerable toxicities. Based on current evidence, fluoropyrimidine-based therapies and the combination of gemcitabine and taxanes were the most effective therapies in the advanced pancreatic cancer, and the combination of immunotherapy and gemcitabine can be developed into a new form of therapy.

Progression-free survival as a surrogate for overall survival in first-line chemotherapy for advanced pancreatic cancer

2016 ◽  
Vol 65 ◽  
pp. 11-20 ◽  
Author(s):  
Tsuyoshi Hamada ◽  
Yousuke Nakai ◽  
Hiroyuki Isayama ◽  
Hideo Yasunaga ◽  
Hiroki Matsui ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Line Chemotherapy

scholarly journals Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

2020 ◽  
Author(s):  
Jiayuan Chen ◽  
Qingling Hua ◽  
Haihong Wang ◽  
Dejun Zhang ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Current Evidence ◽  
First Line ◽  
Similar Treatment ◽  
Treatment Comparison

Abstract Background: Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC) at present. Due to the lack of direct comparison, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. Methods: The eligible retrospective studies of treatments related to modified FOLFIRINOX and GEM-NAB were searched up to 4 April 2020. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study.Results: Twenty-two studies including 6351 patients were involved in this network meta-analysis. The comparisons based on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy. But GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 0.70; 95% CI: 0.51-0.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. Conclusions: Based on current evidence, modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity comparisons. Many factors should be considered for the optimal treatment formulation and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

scholarly journals Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiayuan Chen ◽  
Qingling Hua ◽  
Haihong Wang ◽  
Dejun Zhang ◽  
Lei Zhao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Objective Response ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Current Evidence ◽  
First Line ◽  
Similar Treatment ◽  
Treatment Comparison

Abstract Background Modified FOLFIRINOX and gemcitabine plus nab-paclitaxel (GEM-NAB) have been recommended as first-line therapies for advanced pancreatic cancer (PC). Due to the lack of evidence to directly compare them, we conducted this network meta-analysis to indirectly compare the effectiveness and toxicity of modified FOLFIRINOX and GEM-NAB. Methods The eligible retrospective studies on treatments related to modified FOLFIRINOX and GEM-NAB up to 4 April 2020 were searched and assessed. We used the frequentist model to analyze the survival and toxicity data between different treatments. Pooled analysis for overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and events of toxicity were analyzed in this study. Results Twenty-two studies were involved in this network meta-analysis. The comparisons on OS and PFS showed that modified FOLFIRINOX and GEM-NAB had similar treatment efficacy (OS: 1.13; 95% CI: 0.78–1.63; PFS: HR: 1.19; 95% CI: 0.85–1.67). GEM-NAB was more effective than modified FOLFIRINOX based on the result of ORR (RR: 1.43; 95% CI: 1.04–1.96). Moreover, our analysis showed a similar toxicity profile between modified FOLFIRINOX and GEM-NAB. Conclusions The current evidence showed that modified FOLFIRINOX and GEM-NAB were similar in survival and toxicity. Many factors should be considered for in the formulation of optimal treatment, and our meta-analysis could provide some guidance to treatment selection in the first-line setting for advanced PC.

Progression-free survival as a surrogate endpoint for overall survival in advanced pancreatic cancer: A meta-analysis

Pancreatology ◽  
2016 ◽  
Vol 16 (1) ◽  
pp. S22-S23
Author(s):  
Jianjun Liu ◽  
Qirong Geng ◽  
Pengfei Kong ◽  
Shangxiang Chen ◽  
Xuechao Liu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Free Survival

Efficacy and prognostic significance of triflurodine/tipiracil beyond oxaliplatin and irinotecan based chemotherapy in patients with refractory metastatic colorectal cancer: An observational multicenter study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15586-e15586
Author(s):  
Mohamed Alghamdi ◽  
Shouki Bazarbashi ◽  
Elsamany Shereef ◽  
Mervat Mahrous ◽  
Omar Al shaer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Saudi Arabia ◽  
Neutrophil Count ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
P Value ◽  
Second Line ◽  
First Line ◽  
Free Survival

e15586 Background: In Saudi Arabia, the incidence of colorectal cancer has been increased over the past few years. The optimal treatment beyond the second line is not fully understood. To the best of our knowledge, the efficacy and disease outcomes of triflurodine/tipiracil in Saudi patients with refractory metastatic colorectal cancer(mCRC) has not been studied yet. Our study is a real-life practice evaluation of the efficacy of triflurodine/tipiracil in patients with refractory mCRC. Moreover, the prognosis and the prognostic significance of the different clinical variables have been analyzed. Methods: A retrospective, multi-centers ( 5 centers representative of Saudi Arabia )observational study in patients with mCRC who have received triflurodine/tipiracil beyond oxaliplatin & Irinotecan-based chemotherapy between December 2018-December 2020.We aimed to assess the response to triflurodine/tipiracil, to evaluate the progression-free survival (PFS ), the overall survival (OS), and the associated factors of prognostic significance. Results:The data of 100 patients with refractory mCRC who has received triflurodine/tipiracil have been analyzed. The mean age was 55.2 +11.8 years. Forty-two patients were (42%) females and 58 (58%) were male patients. Sigmoid was the most common primary site of cancer in 35 (35%) patients, followed by rectum 29 (29%). Peritoneal metastasis was present in 17 (23.3%) patients ,liver in 51(56.6%) and lung in 39 (50.7%). Metastatic sites were ≥ 2 in 45 (45%) patients. Metastatic lesions were ≥ 5 in 65 (65%) patients. Xelox chemotherapy regimen was the most commonly used first-line chemotherapy which represents 43%, while Folfiri or Xeliri combination was the most used second line in 57 (60%). For the third line, Folfox or Xelox was used in 81 (83.5%) patients. The fourth line was given to 49 (67.1%). For first-line biological agents, Cetuximab was used most frequently 31 (46.3%).Evaluation of the response to treatment with triflurodine/tipiracil revealed one patient (1%) with a complete response,3 patients (3%) with partial response, 28 (28%) patients with stable disease, and 66 (66%) showed progressive disease. The estimated median progression-free survival was 5 months ( 3.839 - 6.161) and the median overall survival was 12 months (9.732-14.268). The log-rank analysis showed that the baseline neutrophils ≤ 75 % ( P-value= 0.0092) and low hemoglobin level (P-value= 0.0245) were strongly associated with a higher survival. By multivariate Cox regression analysis, the neutrophil count ≤ 75 % was the only independent predictor for survival. Conclusions: Trifluridine/tipiracil is effective in patients with refractory mCRC. The low neutrophil count might predict a better overall survival.

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.

scholarly journals Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis

BMJ ◽  
2019 ◽  
pp. l5460 ◽  
Author(s):  
Yi Zhao ◽  
Jingting Liu ◽  
Xiuyu Cai ◽  
Zhenkui Pan ◽  
Jun Liu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Combination Treatments ◽  
Exon 19 Deletion ◽  
Egfr Mutated

AbstractObjectiveTo compare the efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC).DesignSystematic review and network meta-analysis.Data sourcesPubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and several international conference databases, from inception to 20 May 2019.Eligibility criteria for selecting studiesPublished and unpublished randomised controlled trials comparing two or more treatments in the first line setting for patients with advanced EGFR mutated NSCLC were included in a bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcome measures: progression free survival, overall survival, objective response rate, and adverse events of grade 3 or higher.Results18 eligible trials involved 4628 patients and 12 treatments: EGFR tyrosine kinase inhibitors (TKIs; osimertinib, dacomitinib, afatinib, erlotinib, gefitinib, and icotinib), pemetrexed based chemotherapy, pemetrexed free chemotherapy, and combination treatments (afatinib plus cetuximab, erlotinib plus bevacizumab, gefitinib plus pemetrexed based chemotherapy, and gefitinib plus pemetrexed). Consistent with gefitinib plus pemetrexed based chemotherapy (hazard ratio 0.95, 95% credible interval 0.72 to 1.24), osimertinib showed the most favourable progression free survival, with significant differences versus dacomitinib (0.74, 0.55 to 1.00), afatinib (0.52, 0.40 to 0.68), erlotinib (0.48, 0.40 to 0.57), gefitinib (0.44, 0.37 to 0.52), icotinib (0.39, 0.24 to 0.62), pemetrexed based chemotherapy (0.24, 0.17 to 0.33), pemetrexed free chemotherapy (0.16, 0.13 to 0.20), afatinib plus cetuximab (0.44, 0.28 to 0.71), and gefitinib plus pemetrexed (0.65, 0.46 to 0.92). Osimertinib and gefitinib plus pemetrexed based chemotherapy were also consistent (0.94, 0.66 to 1.35) in providing the best overall survival benefit. Combination treatments caused more toxicity in general, especially erlotinib plus bevacizumab, which caused the most adverse events of grade 3 or higher. Different toxicity spectrums were revealed for individual EGFR-TKIs. Subgroup analyses by the two most common EGFR mutation types indicated that osimertinib was associated with the best progression free survival in patients with the exon 19 deletion, and gefitinib plus pemetrexed based chemotherapy was associated with the best progression free survival in patients with the Leu858Arg mutation.ConclusionsThese results indicate that osimertinib and gefitinib plus pemetrexed based chemotherapy were associated with the best progression free survival and overall survival benefits for patients with advanced EGFR mutated NSCLC, compared with other first line treatments. The treatments resulting in the best progression free survival for patients with the exon 19 deletion and Leu858Arg mutations were osimertinib and gefitinib plus pemetrexed based chemotherapy, respectively.Systematic review registrationPROSPERO CRD42018111954.

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

Efficacy and Safety Of Treatments For Relapsed Or Refractory Mantle Cell Lymphoma (MCL): Results Of a Systematic Literature Review

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5099-5099
Author(s):  
Annete Njue ◽  
Peter C Trask ◽  
Ann Colosia ◽  
Robert Olivares ◽  
Shahnaz Khan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Literature Review ◽  
Systematic Literature Review ◽  
Comparative Studies ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Refractory Disease ◽  
Efficacy And Safety ◽  
Free Survival

Abstract Background MCL accounts for approximately 3%-10% of non-Hodgkin’s lymphoma (NHL) cases. The aggressive course of MCL includes rapid disease progression, with temporary responses to chemotherapy, and a high recurrence rate. However, the clinical course is variable with overall survival ranging from 6 months to more than 10 years. Although the median survival with MCL is 3-4 years, for those with relapsed or refractory disease, survival is much shorter. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory/relapsed MCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were systematically searched for studies assessing the efficacy of safety of treatments for relapsed or refractory MCL published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment withdrawals due to toxicity. Studies had to report on relapsed or refractory MCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report MCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 67 provided relevant data for MCL representing 59 unique studies. Of the 59 studies, 6 were comparative (including 5 RCTs) and 53 were noncomparative single-arm studies; 35 evaluated single-agent regimens, and 24 evaluated combination therapies. A total of 40 different treatments were evaluated in the identified studies. Overall survival and PFS were infrequently reported. Criteria for relapsed or refractory were often not defined, with only 7 studies providing varied definitions. The ORR of active treatments in the few comparative studies ranged from 6%-83%, with most estimates between 45% and 60%. Progression-free survival was approximately 5-7 months with the exception of bortezomib + CHOP in which a 16-month PFS was noted; median OS for these studies ranged from 11-16 months, with 36 months for the aforementioned exception. In the single-arm studies, ORR ranged from 12%-100%, with most estimates from 30%-60%. Progression-free survival was approximately 5-12 months, except for bendamustine alone or in combination (∼21 months) and bortezomib in combination (∼18 months, but with large variability). Overall survival ranged from 12-24 months, with two notable exceptions: bortezomib combination (∼38 months) and temsirolimus in combination with rituximab (∼30 months). Some increase in PFS and OS was observed over the study period. The main safety concerns were related to thrombocytopenia (11-66%), neutropenia (15-100%), anemia (4-34%), and neuropathy (9-13%). Although patients’ MIPI category was collected, outcomes were not reported by this variable. Conclusions The results of this SLR confirm that survival is still low among treatments for relapsed or refractory MCL making this a continued area of unmet need. The small number of randomized trials makes it difficult to identify a standard of care. The lack of common treatments among the randomized controlled trials for MCL and the variability in the populations studied did not allow for a valid meta-analysis. Small sample size, infrequent reporting of OS/PFS, limited information on prior treatments/responses, and patient characteristics also make comparison of results difficult. Comparative studies demonstrating relative survival advantages of various therapies in relapsed or refractory MCL are needed, as is more information on the relation between MIPI scores and outcomes. In the absence of such evidence, management of relapsed or refractory disease should be based on individual patient characteristics and concerns regarding tolerability. Disclosures: Njue: RTI Health Solutions: Employment. Trask:Sanofi: Employment. Colosia:RTI Health Solutions: Employment. Olivares:Sanofi: Employment. Khan:RTI Health Solutions: Employment. Abbe:Sanofi: Employment. Police: RTI Health Solutions: Employment. Wang:RTI Health Solutions: Employment. Sherrill:RTI Health Solutions: Employment. Kaye:RTI Health Solutions: Employment. Awan:Lymphoma Research Foundation (Career Development Award): Research Funding.

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