scholarly journals Adverse events of different chemotherapy regimens in the first-line treatment of patients with advanced or metastatic urothelial cancer: A systematic review and network meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Ekaterina Laukhtina ◽  
Keiichiro Mori ◽  
Hadi Mostafaei ◽  
Axel S. Merseburger ◽  
Peter Nyirady ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Urothelial Cancer ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
First Line ◽  
Randomized Controlled ◽  
Metastatic Urothelial Cancer ◽  
First Line Treatment

scholarly journals Different Chemotherapy Regimens in the Management of Advanced or Metastatic Urothelial Cancer: a Bayesian Network Meta-Analysis of Randomized Controlled Trials

2018 ◽  
Vol 50 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Yi Wang ◽  
Lingyan Xu ◽  
Xianghu Meng ◽  
Zhiqiang Qin ◽  
Yamin Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Urothelial Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Credible Interval ◽  
Controlled Trials ◽  
First Line ◽  
Randomized Controlled ◽  
Metastatic Urothelial Cancer

Background/Aims: Urothelial cancer (UC) as a chemotherapy-sensitive tumor, has achieved remarkable progresses in therapeutic paradigm, particularly in the advanced/metastatic stages. However, both clinicians and patients are confused when it comes to choosing the optimal chemotherapy. Hence, this article was aimed to conduct a comprehensive comparison of different chemotherapy regimens for advanced or metastatic UC in terms of survival benefits or adverse events. Methods: The online databases PubMed, EMBASE and Web of Science were searched systematically and comprehensively for randomized controlled trials (RCTs) up to September 15, 2017. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% credible interval (CrI) were calculated by Markov chain Monte Carlo methods. The effectiveness and safety of included regimens were conducted to provide a hierarchy by means of rank probabilities with the help of “R-3.4.0” software and the “gemtc-0.8.2” package. The surface under the cumulative ranking curve (SUCRA) was also incorporated in our analysis for ranking the corresponding chemotherapy regimens. Results: Ten different chemotherapy regimens involved in this article were predominantly of trials in a first-line setting, and eight clinical outcomes were ultimately analyzed in this study. In terms of Overall response rate (ORR), Overall survival (OS) or Progression-free survival (PFS)/Time to progression (TTP), the rank probabilities and SUCRA indicated that Paclitaxel/cisplatin/gemcitabine (PCG) was superior to gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), the traditional first-line treatment for advanced/metastatic UC. In the case of ORR or PFS/TTP, GC+sorafenib also displayed its superiority in comparison with GC or MVAC. Despite their survival benefits, PCG or GC+sorafenib presented a relatively higher incidence of adverse events. Conclusion: Our results revealed that by adding a paclitaxel or sorafenib into the first-line GC, it could yield a better survival benefit, but also worsen adverse events for advanced/ metastatic UC. Clinically, physicians should weigh the merits of these approaches to maximize the survival benefits of eligible patients.

Safety profile of immune checkpoint inhibitors versus sorafenib as first-line treatment in advanced hepatocellular carcinoma: A meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 315-315
Author(s):  
Alessandro Rizzo ◽  
Giorgio Frega ◽  
Angela Dalia Ricci ◽  
Andrea Palloni ◽  
Simona Tavolari ◽  
...  
Keyword(s):  
Safety Profile ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
Randomized Controlled ◽  
First Line Treatment

315 Background: Systemic treatment with tyrosine kinase inhibitors such as sorafenib represents the mainstay of advanced-stage hepatocellular carcinoma (HCC). However, survival outcomes remain disappointing, mostly because of the onset of acquired resistance and a suboptimal safety profile, which frequently requires treatment modifications and early discontinuation of treatment – thus, interfering with compliance and long-term outcomes of patients. With immune checkpoint inhibitors (ICIs) quickly expanding as a novel therapeutic option in advanced HCC, the toxicity profiles of these agents should be kept in mind. We performed a meta-analysis with the aim to compare all-grade (G) adverse drug events (ADEs) of ICIs (alone or in combination with other anticancer agents) versus sorafenib monotherapy across randomized controlled trials (RCTs) of first-line treatment for advanced HCC. Methods: Eligible studies included RCTs comparing ICIs versus sorafenib as first-line treatment in HCC. Safety profile from each selected study was investigated for all-G most common ADEs. Outcomes of interest were as follows: pruritus, diarrhea, hand-foot skin reaction (HFSR), fatigue, aspartate aminotransferase (AST) increase, rash, hypertension and decreased appetite. Results were compared by calculating odds ratios (ORs) with 95% confidence intervals (CIs); ORs were combined with Mantel-Haenszel method. All statistical analyses were performed using R studio software. Results: Two RCTs (CheckMate 459, IMbrave 150) involving 1,228 patients were included in the analysis. Patients treated with ICIs showed higher risk of pruritus (OR 1.99, 95% CI = 1.22-3.24) while sorafenib treatment was associated with higher risk of diarrhea (OR 0.26, 95% CI = 0.18-0.37) and HFSR (OR 0.01, 95% CI = 0-0.04). Conversely, no statistically significant differences were observed in terms of fatigue (OR 0.84, 95% CI = 0.45-1.58), AST increase (OR 1.21, 95% CI = 0.78-1.88), rash (OR 0.71, 95% CI = 0.46-1.11), hypertension (OR 0.28, 95% CI = 0.01-9.76) and decreased appetite (OR 0.41, 95% CI = 0.14-1.21) between the two groups. Conclusions: Although the substantial heterogeneities affecting our analyses, ICIs appear feasible in advanced HCC, being endowed with an acceptable safety profile. Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in advanced HCC.

scholarly journals First-Generation EGFR-TKI Plus Chemotherapy Versus EGFR-TKI Alone as First-Line Treatment in Advanced NSCLC With EGFR Activating Mutation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Qiang Wu ◽  
Wuxia Luo ◽  
Wen Li ◽  
Ting Wang ◽  
Lin Huang ◽  
...  
Keyword(s):  
First Generation ◽  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Line Treatment ◽  
First Line ◽  
Randomized Controlled ◽  
Egfr Tki ◽  
First Line Treatment

ObjectiveThe aim of this meta-analysis was to evaluate efficacy and toxicity of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy (CT) compared to EGFR-TKI monotherapy as first-line treatment in advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutation.MethodsA systematic literature search of randomized controlled trials using Cochrane Library, PubMed, Embase, and Web of Science, was performed up to Jan. 7th, 2020. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated as effect values for progress-free survival (PFS) and overall survival (OS). Risk ratio (RR) and Odds ratio (OR) were calculated as effect values for objective response rate (ORR) and toxicity, respectively.ResultsA total of eight randomized trials involving 1,349 advanced NSCLC patients with sensitive EGFR mutation were included in the meta-analysis. All patients in both groups received first-generation TKI as first-line treatment. The pooled HR of PFS and OS was 0.56 (95% CI = 0.50–0.64; P <0.00001) and 0.70 (95% CI = 0.54–0.90; P = 0.005), respectively. Subgroup analysis showed significantly higher OS advantages in patients receiving doublet CT (P = 0.02) and concurrent therapy (P = 0.002). The ORR in the EGFR-TKI plus CT group was significantly higher than in the EGFR-TKI monotherapy group (RR = 1.18, 95% CI = 1.10–1.26). The combination regimen showed a higher incidence of chemotherapy-induced toxicities. Subgroup analysis indicated that doublet chemotherapy rather than single-agent chemotherapy significantly increased incidence of grade 3 or higher leukopenia, neutropenia and anemia.ConclusionsCompared with EGFR-TKI monotherapy, the combination of first-generation EGFR-TKI and CT, especially when applying concurrent delivery of platinum-based doublet chemotherapeutic drugs, significantly improve ORR and prolong PFS and OS in first-line treatment for advanced EGFR-mutated NSCLC. Although increasing incidence of chemotherapy-induced toxicities occurs in the combination group, it is well tolerated and clinically manageable.

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