Systematic review and network meta-analysis of first-line treatments in mRCC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16086-e16086
Author(s):  
Barbara Elizabeth Ratto ◽  
Sutirtha Chakraborty ◽  
Harini Chinthapatla ◽  
Manik Kalra
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Mixed Treatment Comparison ◽  
First Line ◽  
Eligibility Criteria ◽  
Treatment Comparison ◽  
Poor Risk ◽  
Treatment Naïve ◽  
Risk Patients

e16086 Background: The approval of newer agents in metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm in first-line settings. The aim of this review was to compare pazopanib against current first-line treatments in RCC. Methods: A systematic review was conducted that assessed pazopanib against first-line agents in treatment naïve patients with mRCC. Relevant databases and conferences were searched to identify randomized controlled trials (RCTs) assessing treatment naïve adult patient (≥18 years). Frequentist mixed treatment comparison (MTC) method was applied for the pairwise comparisons among treatments for ITT population and favorable, intermediate, and poor risk subgroups. Results: Twenty-three RCTs met the eligibility criteria. The MTC results showed that pazopanib was comparable to sunitinib in terms of progression free survival (PFS) and overall survival (OS) in ITT population. Cabozantinib was significantly better compared to pazopanib for PFS; however, there was heterogeneity in the patient population. Pazopanib was comparable to nivolumab + ipilimumab when assessed for PFS in ITT population; although, favorable risk patients treated with pazopanib achieved significantly higher PFS compared to nivolumab + ipilimumab (HR: 0.46, 95% CI: [0.37, 0.57]). Atezolizumab + bevacizumab and avelumab + axitinib were associated with significantly higher PFS compared to pazopanib. Cabozantinib and nivolumab + ipilimumab were associated with better OS compared to pazopanib. Conclusions: The newer agents i.e. cabozantinib and nivolumab + ipilimumab are approved for intermediate/poor risk patients. The results suggests that pazopanib is still a reliable option for treatment of patients in first-line settings, especially for favorable/intermediate risk patients.[Table: see text]

scholarly journals First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and meta-analysis

2020 ◽  
Vol 4 (12) ◽  
pp. 2723-2735 ◽  
Author(s):  
Claudia Vener ◽  
Rita Banzi ◽  
Federico Ambrogi ◽  
Annalisa Ferrero ◽  
Giuseppe Saglio ◽  
...  
Keyword(s):  
Systematic Review ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Philadelphia Chromosome ◽  
Chronic Phase ◽  
Progression Free Survival ◽  
Third Generation ◽  
Newly Diagnosed ◽  
First Line ◽  
Eligibility Criteria

Abstract Imatinib, the first tyrosine kinase inhibitor (TKI) for the treatment of chronic myeloid leukemia (CML), improves overall survival (OS), but the introduction of newer TKIs requires the definition of the optimal first-line TKI for newly diagnosed Philadelphia chromosome–positive (Ph+) chronic-phase (CP) CML. This systematic review of randomized controlled trials (RCTs) compares the efficacy and safety of imatinib vs second-generation (dasatinib, nilotinib, bosutinib) and third-generation TKIs (ponatinib) in adults with newly diagnosed Ph+ CP CML, concentrating on OS, progression-free survival (PFS), and hematological and nonhematological adverse events. The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. Seven RCTs published between 1990 and 2019 (involving 3262 participants) satisfied the eligibility criteria. Two RCTs (imatinib vs nilotinib and imatinib vs dasatinib) found no difference in 5-year OS or PFS. Second- and third-generation TKIs improved 3-month major molecular responses (relative risk [RR], 4.28; 95% confidence interval [CI], 2.20-8.32) and other efficacy outcomes, decreased accelerated/blastic-phase transformations (RR, 0.44; 95% CI, 0.26-0.74), but were associated with more cases of thrombocytopenia (RR, 1.57; 95% CI, 1.20-2.05), cardiovascular events (RR, 2.54; 95% CI, 1.49-4.33), and pancreatic (RR, 2.29; 95% CI, 1.32-3.96) and hepatic effects (RR, 3.51; 95% CI 1.55-7.92). GRADE showed that the certainty of the evidence ranged from high to moderate. This study shows that, in comparison with imatinib, second- and third-generation TKIs improve clinical responses, but the safer toxicity profile of imatinib may make it a better option for patients with comorbidities.

Comparative Efficacy of First Line Treatment of Chronic Myeloid Leukaemia (CML): A Systematic Review and Meta-Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3436-3436 ◽  
Author(s):  
Stuart Mealing ◽  
Leticia Barcena ◽  
Neil Hawkins ◽  
James Clark ◽  
Catherine Davis
Keyword(s):  
Systematic Review ◽  
Standard Dose ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Newly Diagnosed ◽  
First Line ◽  
Treatment Comparison ◽  
2Nd Generation ◽  
Mixed Treatment ◽  
Better Than

Abstract Abstract 3436 Introduction: Historically, interferon-alpha, hydroxyurea or chemotherapy were used as first line therapy for individuals newly diagnosed with CML. Current practice, however, recommends that tyrosine-kinase inhibitors (TKIs) be used in this patient group, with imatinib (1st generation TKI) being the current standard of care. Recent publications provide data from randomized clinical trials on 2nd generation TKIs (dasatinib and nilotinib) in the first-line setting. In the absence of randomized head to head evidence for all three TKI's, a Bayesian mixed treatment comparison meta-analysis provides a means of indirectly estimating the treatment effect of one intervention relative to another. Methods: A systematic review identified RCTs that reported or summarized efficacy data for any of the treatments of interest in treatment-naive CML patients. In order to maximise the evidence network, RCT's of non-TKI's were also included in the review. Where reported, data was extracted for molecular, hematological and cytogenic response at three montly intervals. In addition, safety and progression free and overall survival data was extracted for all reported timepoints. Extracted data was analyzed in a Bayesian mixed treatment comparison using a fixed-effects model. The outputs from all analyses were expressed as odds ratios with Imatinib 400mg SID used as the baseline intervention in all analyses. Results: Overall, 44 articles arising from 19 distinct clinical trials were included in the review. The results for complete cytogenetic response (CCyR) at twelve months (expressed as both response probabilities and odds ratios) are presented in table 1. High dose imatinib performed no better than standard dose imatinib. However, response with both 2nd generation TKIs was significantly better than with standard dose imatinib with the effect size being doubled on all endpoints. Head to head results for nilotinib and dasatinib showed no statistically significant differences (p=0.05) between the two products on all endpoints (see table 2). Conclusions: Compared to Imatinib, the use of 2nd generation TKI's for the treatment of newly diagnosed CML results in a significant improvement in complete cytogenic response. However, the current evidence base is not rich enough to distinguish between the two 2nd generation TKIs either in terms of response or progression free survival. The analyses presented will be strengthened by the inclusion of additional RCT data that may become available in the future. Disclosures: Mealing: Oxford Outcomes: Employment. Barcena:Oxford Outcomes: Employment. Hawkins:Oxford Outcomes: Employment. Clark:Oxford Outcomes: Employment. Davis:Bristol Myers-Squibb: Employment.

scholarly journals Comparative efficacy of dabrafenib + trametinib versus treatment options for metastatic melanoma in first-line settings

2021 ◽  
Author(s):  
Jing Wu ◽  
Jaydeep Das ◽  
Manik Kalra ◽  
Barbara Ratto
Keyword(s):  
Metastatic Melanoma ◽  
Survival Data ◽  
Meta Analysis ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Comparable Efficacy ◽  
First Line ◽  
Eligibility Criteria ◽  
Term Survival ◽  
Treatment Naïve

Aim: The objective was to systematically review the literature and assess the relative efficacy of agents approved in first-line settings via network meta-analysis. Materials & methods: A literature review was conducted via searching different medical databases. The eligibility criteria included Phase II or III randomized controlled trials that had enrolled treatment-naive adult patients with advanced/metastatic melanoma. Results: The network meta-analysis results suggested that dabrafenib + trametinib significantly prolongs the survival outcomes compared with the monotherapies and had comparable efficacy profile compared with encorafenib + binimetinib and cobimetinib + vemurafenib. In comparison with immunotherapies, the results varied for progression-free survival and overall survival. Conclusion: Long-term survival data of dabrafenib + trametinib establishes the combination as one of the preferred treatment options for previously untreated melanoma patients.

scholarly journals Real-world comparative effectiveness of nab-paclitaxel plus gemcitabine versus FOLFIRINOX in advanced pancreatic cancer: a systematic review

2019 ◽  
Vol 11 ◽  
pp. 175883591985036 ◽  
Author(s):  
Elena Gabriela Chiorean ◽  
Winson Y. Cheung ◽  
Guido Giordano ◽  
George Kim ◽  
Salah-Eddin Al-Batran
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Real World ◽  
Controlled Trial ◽  
Safety Data ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
First Line ◽  
Eligibility Criteria ◽  
Grade 3

Background: No clinical trial has directly compared nab-paclitaxel/gemcitabine (nab-P/G) with FOLFIRINOX (fluorouracil/leucovorin/oxaliplatin/irinotecan) in metastatic or advanced pancreatic cancer (mPC or aPC). We conducted a systematic review of real-world studies comparing these regimens in the first-line setting. Methods: Embase and MEDLINE databases through 22 January 2019, and Gastrointestinal Cancers Symposium 2019 abstracts were searched for real-world, retrospective studies comparing first-line nab-P/G versus FOLFIRINOX in mPC or aPC that met specific parameters. Studies with radiotherapy were excluded. Study quality was assessed using the Newcastle–Ottawa Scale. Results: Of 818 records initially identified, 35 were duplicates and 749 did not meet the eligibility criteria, mostly because they were either not comparative ( n = 356) or not first line ( n = 245). The remaining 34 studies (21 mPC; 13 aPC) assessed >6915 patients who received nab-P/G or FOLFIRINOX. In the studies identified, the median overall survival (OS) reached 14.4 and 15.9 months with nab-P/G and FOLFIRINOX, respectively, and median progression-free survival reached 8.5 and 11.7 months, respectively. Safety data were reported in 14 studies (2205 patients), including 8 single-institutional studies. In most single-institutional studies that reported safety data, rates were higher with FOLFIRINOX versus nab-P/G for grade 3/4 neutropenia (five of six studies) and febrile neutropenia (all three studies), while rates of grade 3/4 peripheral neuropathy were higher with nab-P/G in four of seven studies. Conclusions: Although FOLFIRINOX was associated with slightly longer median OS in more studies, the differences, when available, were not statistically significant. Therefore, a randomized, controlled trial is warranted. Toxicity profile differences represent key considerations for treatment decisions.

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.

scholarly journals Efficacy of First Line Systemic Chemotherapy and Multikinase Inhibitors in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Songporn Oranratnachai ◽  
Sasivimol Rattanasiri ◽  
Anantaporn Pooprasert ◽  
Amarit Tansawet ◽  
Thanyanan Reungwetwattana ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Optimal Choice ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Mixed Effect ◽  
Multikinase Inhibitors ◽  
Treatment Naïve ◽  
Randomised Controlled

BackgroundHepatocellular carcinoma (HCC) is the third most fatal cancer, with a 5-year survival rate of 18%. Standard frontline-therapy is multikinase inhibitors (MKIs), but accessibility is still limited, particularly in developing countries. This network meta-analysis (NMA) aimed to compare the efficacy of usual chemotherapy vs MKIs.MethodRandomised-controlled trials (RCTs) comparing any among chemotherapy vs MKIs in treatment-naïve patients with advanced HCCs were identified from MEDLINE and SCOPUS databases. Overall survival (OS) and progression-free survival (PFS) probabilities and times were extracted from Kaplan-Meier curves using Digitizer, and then converted to individual patient time-to-event data. A one-stage mixed-effect survival model was applied to estimate median OS and PFS. A two-stage NMA was applied for the overall response rate and adverse events (AEs) outcome.ResultsA total of 20 RCTs were eligible for NMA. Lenvatinib was the best treatment among single MKIs, with median OS and PFS of 9 and 6.3 months, without significant differences in AEs relative to other MKIs. Median OS and PFS were 0.70 (-0.42, 1.83) and 2.17 (1.41, 2.93) months longer with Lenvatinib than Sorafenib. Among chemotherapy agents, FOLFOX4 had the longest median OS and PFS at 7.9 and 4.3 months, respectively, without significant AEs compared to other chemotherapies. The combination of Sorafenib+Doxorubicin prolonged median OS and PFS to 12.7 and 6.3 months, respectively.ConclusionUse of the MKIs Lenvatinib or Sorafenib as first line systemic treatment for advanced HCC could be beneficial. However, FOLFOX4 might be the optimal choice in a developing country where the health-care budget is limited.

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