A systematic review of post first-line treatments for advanced gastrointestinal stromal tumor (GIST): Direct pairwise meta-analyses and indirect comparisons.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 195-195
Author(s):  
Keya Shah ◽  
Kelvin K. Chan ◽  
Yoo-Joung Ko
Keyword(s):  
Systematic Review ◽  
Indirect Comparison ◽  
Phase Iii ◽  
Controlled Trials ◽  
First Line ◽  
The Third ◽  
Third Line ◽  
Line Setting ◽  
Meta Analyses ◽  
Indirect Comparisons

195 Background: Treatment for metatastatic or unresectable GIST is with imatinib. The majority of patients eventually acquire imatinib resistance, prompting the development of a growing number of agents as post-first-line treatment. Currently no studies directly compare these treatments. Methods: A systematic review was performed through MEDLINE, EMBASE, CENTRAL, and ASCO meeting abstracts up to July 2014 to identify randomized controlled trials that included GIST patients who were previously treated with a first-line chemotherapy for advanced disease. Progression-free survival (PFS) and overall survival (OS) with 95% credible regions were extracted using the Parmar method. Direct pairwise meta-analyses and indirect comparisons using the Bucher method were performed. Results: Four studies were identified for the systematic review. 1 study (n=312) showed that sunitinib in the second-line setting (vs. placebo) improved PFS but not OS. 3 studies (n=528) examined the third-line setting (imatinib resumption vs. placebo; regorafenib vs. placebo; nilotinib vs. best supportive care with or without imatinib or sunitinib). Of the 3 third-line studies, there was significant heterogeneity between placebo-controlled trials and the non-placebo controlled trial (I2= 98%). Direct pairwise meta-analysis using random-effects of the 2 placebo-controlled studies showed that the PFS hazard ratio (HR) was 0.63 (0.22-0.61, p=0.0001), whereas the PFS HR for the non-placebo controlled study was 0.90 (0.65-1.26, p=0.56). These 2 HRs are different statistically (interaction: p=0.002). Indirect comparisons of imatinib resumption vs. regorafenib suggested that the PFS HR was 0.59 (0.31-1.11, p=0.10), trending in favor of regorafenib. OS HRs were not significant for direct or indirect comparison in the third-line setting. Conclusions: The number and size of completed phase III studies and the lack of a standard comparator arm limit the use of direct and indirect comparison methods to determine the best therapeutic option for patients who have progressed on imatinib. At this time, clinicians should interpret the available evidence at an individual level.

scholarly journals A systematic review and network meta-analysis of post-imatinib therapy in advanced gastrointestinal stromal tumour

2017 ◽  
Vol 24 (6) ◽  
pp. 531 ◽  
Author(s):  
K. Shah ◽  
K.K.W. Chan ◽  
Y.J. Ko
Keyword(s):  
Systematic Review ◽  
Gastrointestinal Stromal Tumour ◽  
Stromal Tumour ◽  
Controlled Trials ◽  
First Line ◽  
Imatinib Resistance ◽  
The Third ◽  
Third Line ◽  
Line Setting ◽  
Indirect Comparisons

Background The standard first-line systemic therapy for advanced gastrointestinal stromal tumour (gist) is imatinib. However, most gists develop imatinib resistance, highlighting the need for new agents in the imatinib-refractory setting. Currently, no randomized studies have directly compared the available post–firstline treatments.Methods In a systematic review, the medline, embase, and central databases, and American Society of Clinical Oncology abstracts to July 2014 were searched to identify randomized controlled trials that included gist patients treated with post–first-line therapies. Hazard ratios (hrs) for progression-free (pfs) and overall survival (os) were extracted. Direct pairwise meta-analyses and indirect comparisons using the Butcher method were performed.Results Four studies were identified for the systematic review. One study showed that sunitinib in the second-line setting (vs. placebo) was associated with improved pfs, but not improved os. Three studies examined the third-line setting (imatinib resumption vs. placebo, regorafenib vs. placebo, nilotinib vs. best supportive care). In the third-line settings, the two placebo-controlled and the non-placebo-controlled trials showed significant heterogeneity (I2 = 98%). Indirect comparisons of imatinib resumption and regorafenib suggested that the hr for pfs was 0.59 (95% confidence interval: 0.31 to 1.12; p = 0.10), trending in favour of regorafenib. Indirect comparisons found that toxicities were higher in the regorafenib group, with a risk difference of 27.8% for any-grade toxicities and 19.5% for grades 3 and 4 toxicities.Conclusions Because a head-to-head study of imatinib resumption compared with regorafenib is unlikely ever to be conducted, our study suggests that, in terms of pfs, regorafenib might be the preferred treatment. However, given the increased toxicity observed with regorafenib, clinicians should interpret that evidence with caution at an individual patient level.

scholarly journals P33.15 TMB in the First-Line Setting of NSCLC: A Systematic Review with Indirect Comparisons Between PD-1 and PD-L1 Inhibitors

2021 ◽  
Vol 16 (3) ◽  
pp. S411-S412
Author(s):  
V. Gristina ◽  
A. Galvano ◽  
M. Castiglia ◽  
A. Perez ◽  
N. Barraco ◽  
...  
Keyword(s):  
Systematic Review ◽  
First Line ◽  
Line Setting ◽  
Indirect Comparisons

Survival post-progression (SPP) in phase III trials of chemotherapy in advanced NSCLC: Its potentially different impact on OS in the first-line and salvage settings.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18027-e18027
Author(s):  
Katsuyuki Hotta ◽  
Nagio Takigawa ◽  
Yoshiro Fujiwara ◽  
Akiko Hisamoto ◽  
Eiki Ichihara ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Coefficient Of Determination ◽  
Steady Increase ◽  
First Line ◽  
Phase Iii Trials ◽  
Third Line ◽  
Line Setting ◽  
The Relationship ◽  
Line Chemotherapy

e18027 Background: We previously demonstrated that in advanced NSCLC, survival after progression to first-line chemotherapy (SPP-1) has significantly improved and has become more closely associated with OS after the initiation of first-line chemotherapy (OS-1), potentially because of the recent development of active agents even in salvage settings (Plos One 2011). We conducted a literature survey to examine time trend in survival after progression to second- or third-line chemotherapy (SPP-2/3) and its potential correlation with OS after the initiation of second- or third-line chemotherapy (OS-2/3). Methods: SPP-2/3 was pragmatically defined in each second- or third-line chemotherapy trial as the interval of MST (OS-2/3) minus median PFS time (PFS-2/3) (OS-2/3 = PFS-2/3 + SPP-2/3). The relationship between PFS-2/3 and OS-2/3 or SPP-2/3 and OS-2/3 was assessed in the regression analysis using the coefficient of determination (r2); higher r2 means a higher correlation. Results: Twenty trials of the second- or third-line chemotherapy initiated between 2001 and 2009, were defined (14,951 patients, 37 chemotherapy arms). Contrary to our previous findings regarding SPP-1, SPP-2/3 has not been significantly prolonged over the years (8.0-day increase per year; p = 0.161) despite a steady increase in OS-2/3 (17.2-dayincrease per year; p = 0.003) and PFS-2/3 (9.8-day increase per year; p = 0.005). Overall, a moderate association was observed between OS-2/3 and SPP-2/3 (r2 = 0.6755), suggesting SPP-2/3 could predict 68% of the variation in OS-2/3. Interestingly, the association between OS-2/3 and SPP-2/3 became less close over the years (r2 = 0.9849, 0.8280, and 0.5667 in 2001–2003, 2004–2006, and 2007–2009, respectively). Conclusions: During the period SPP-2/3 seemed stable, and the association between SPP-2/3 and OS-2/3 has become unclear probably because of recent survival improvement in PFS-2/3 rather than SPP-2/3. This seems in contrast with our previous report that SPP-1 has become more tightly associated with OS-1 over the year, potentially due to the establishment of active post-study treatments just in second- or third-line setting.

scholarly journals Comparative Efficacy and Safety of Programmed Death-1 Pathway Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Network Meta-Analysis of Phase III Clinical Trials

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2614
Author(s):  
Laercio Lopes da Silva ◽  
Pedro Nazareth Aguiar ◽  
Robin Park ◽  
Eduardo Edelman Saul ◽  
Benjamin Haaland ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Success Rates ◽  
First Line ◽  
Phase Iii Clinical Trials ◽  
Third Line ◽  
Line Setting

Background: The use of checkpoint inhibitors has changed the treatment landscape for gastroesophageal cancer in the third-line setting. However, success rates in earlier treatment lines are highly variable across trials. Herein, we compare the efficacy and safety of the different anti-PD-1/PD-L1 regimens with or without chemotherapy; Methods: We performed a network meta-analysis (NMA) of anti-PD-1/PD-L1 monotherapy or combined with chemotherapy (chemoimmunotherapy) for gastroesophageal cancers without ERBB2 overexpression; Results: The first-line NMA included four trials (N = 3817), showing that chemoimmunotherapy improved OS and PFS without significant safety difference: Nivolumab-chemotherapy, OS (HR: 0.83 [95% CI, 0.75–0.92]), PFS (HR 0.68 [95% CI, 0.57–0.81]), Pembrolizumab-chemotherapy: OS (HR 0.77 [95% CI, 0.67–0.88]), PFS (HR: 0.72 [95% CI, 0.60–0.85]. Pembrolizumab monotherapy was the safest first-line treatment, SAE (OR 0.02 [95% CI, 0.00–0.2]) but showed no survival benefit. The second-line NMA encompassed four trials (N = 2087), showing that anti-PD-1 significantly improved safety but not survival: camrelizumab, SAE (OR 0.37; [95% CI, 0.24–0.56]); nivolumab, SAE (OR 0.13, [95% CI, 0.08–0.2]) pembrolizumab, SAE (OR 0.4; [95% CI, 0.30–0.53]); Conclusions: chemoimmunotherapy improves OS and PFS in previously untreated gastroesophageal cancers. Anti-PD-1 monotherapies improve safety in refractory disease, with no significant survival benefit.

Comparison of systemic therapy efficacy in advanced hepatocellular carcinoma: Systematic review and frequentist network meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 293-293
Author(s):  
Robin Park ◽  
Laércio Lopes da Silva ◽  
Voravech Nissaisorakarn ◽  
Ivy Riano ◽  
Anwaar Saeed
Keyword(s):  
Hepatocellular Carcinoma ◽  
Systematic Review ◽  
Meta Analysis ◽  
Objective Response ◽  
Indirect Comparison ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
First Line ◽  
Line Setting ◽  
Systemic Agents

293 Background: Several systemic agents are approved for use in the first line and second line treatment settings for advanced hepatocellular carcinoma (aHCC). However, choosing among available options in both first and second line settings remain difficult due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings. Methods: Published clinical trials that have evaluated systemic agents in the first line and second line settings in advanced HCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and abstracts presented in the main annual ASCO and ESMO conferences from 2017 to 2020. Studies published in English providing clinical outcomes data including overall survival (OS), progression free survival (PFS) and objective response rate (ORR) were included in the analysis. The primary outcomes of interest were pooled hazard ratios (HR) of OS and OR of ORR in first line studies and HR of PFS and OR of ORR for second line studies. OS for second line agents were synthesized in a qualitative analysis. Results: Overall, 8,335 patients (13 studies) and 4,612 patients (11 studies) were analyzed in phase II/III trials for first line and second line settings respectively. In the first line setting, atezolizumab plus bevacizumab and lenvatinib were ranked highest as the regimens associated with the greatest OS (A+B, HR 0.58, 95% CI, 0.42-0.80; P-score 0.993) and ORR (lenva, OR 3.34, 95% CI, 2.17-5.14; P-score 0.080) respectively. In the second line setting, cabozantinib showed the highest probability of greatest PFS benefit (HR 0.44, 95% CI, 0.29-0.66; P-score 0.854) as well as the highest probability of greatest ORR benefit (cabo, OR 9.40, 95% CI, 1.25-70.83, P-score, 0.266). Conclusions: In the first line setting, atezolizumab plus bevacizumab may be the superior regimen whereas lenvatinib may be considered as the initial option when robust tumor responses are preferred. In the second line setting, cabozantinib may be the preferred option including in cases when robust tumor responses are favored.

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