Anti PD-(L)1 in KRAS mutant advanced nsclcs: A meta-analysis of randomized controlled trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9025-9025
Author(s):  
Thierry Landre ◽  
Gregoire Justeau ◽  
Jean-baptiste Assié ◽  
Kader Chouahnia ◽  
Chérifa Taleb ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Second Line ◽  
Wild Type ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
Meta Analyses ◽  
Review Manager

9025 Background: KRAS comprise the most frequently found oncogene driver mutation in non-small cell lung cancer (NSCLC), accounting for 20-25% of these patients. Single-agent Anti PD-(L)1 clinical efficacy against KRAS mutant NSCLC is a topic of debate. Methods: This meta-analysis examined randomized-trial data comparing first-or second line Anti PD-(L)1 +/- chemotherapy (CT) vs CT alone for KRAS mutant advanced NSCLCs. Outcome measures included overall survival (OS) and progression-free survival (PFS). Analyses were computed using the Cochrane method of collaboration for meta-analyses, with Review Manager software (RevMan version 5.3; Oxford, UK). Results: We analyzed 3 trials in first line (IMPOWER-150, KEYNOTE-189 and KEYNOTE-042), as well as 3 trials in second line (OAK, POPLAR and CHECKMATE-057) including 1313 NSCLCs (386 KRAS mutant and 927 KRAS wild-type tumor). Anti PD-(L)1 +/- CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS (0.59 [0.49-0.72]; p < 0.00001) and PFS (0.58 [0.43-0.78]; p = 0.0003) compared to CT alone in KRAS mutant NSCLCs. Survival benefits occured in both first and second line. Survival benefits observed in KRAS wild-type NSCLCs were (0.87 [0.76-0.99]; p = 0.03) and (0.79 [0.56-1.11]; p = 0.17) respectively. OS benefit in KRAS mutant was significantly superior compared to OS benefit in KRAS wild-type (p = 0,001). Conclusions: Anti PD-(L)1 (+/- CT) appears superior to CT alone both for mutant and wild-type KRAS in advanced NSCLCs for OS and PFS with higher magnitude of benefit in KRAS mutated group for OS.

scholarly journals Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis

2021 ◽  
Author(s):  
Antonio Giovanni Solimando ◽  
Nicola Susca ◽  
Antonella Argentiero ◽  
Oronzo Brunetti ◽  
Patrizia Leone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Randomized Controlled ◽  
Meta Analyses

Abstract Background & Aims A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option. Methods Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels. Results Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification. Conclusions The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.

Anti-PD-1/PD-L1 plus chemotherapy versus chemotherapy alone in first-line treatment for patients with metastatic NSCLC that were PD-L1 negative or less than 1%.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9061-9061
Author(s):  
Thierry Landre ◽  
Gaetan Des Guetz ◽  
Kader Chouahnia ◽  
Cherifa Taleb ◽  
Alain Vergnenegre ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival ◽  
Study Heterogeneity ◽  
Duration Of Response ◽  
Line Setting

9061 Background: Clinical efficacy of single agent anti-PD-1/PD-L1 in patients with Non-Small-Cell-Lung-Cancer (NSCLC) that were PD-L1 negative or < 1% is controversial. Recent studies have evaluated the combination of anti-PD-1/PD-L1 to chemotherapy (CT) for this population in the first line setting. Methods: We performed a meta-analysis (MA) of randomized trials that compared PD-1/PD-L1 inhibitor plus CT with CT alone in first line of treatment for advanced NSCLC. The outcomes included overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with undetectable PD-L1 expression or < 1%. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. Results: Four studies evaluated atezolizumab + CT (IMpower 130,131,132 and 150), three studies pembrolizumab + CT (Keynote 021, 189 and 407) and one study evaluated nivolumab + CT (CheckMate 227). The eight eligible studies included 2037 patients (1246 with PD-L1 negative and 791 with PD-L1 expression < 1%). Most of the patients were men and smokers, with a median age of 64 years. There were 1423 Non-squamous (69.8 %) and 614 Squamous tumors (30%). The combination (PD-1/PD-L1 inhibitor + CT) was significantly associated with improvement of OS (hazards ratio [HR], 0.75; 95% CI 0.63–0.89; p < 0.0001), PFS (HR, 0.72; 95% CI 0.65–0.80; p < 0.0001) and ORR (relative ratio [RR], 2.59; 95% CI 1.46–4.60; p < 0.0001). Moreover, median duration of response (DOR) was statistically longer with combination (8.1 months versus 4.9; p < 0.0008). Conclusions: For patients with untreated NSCLC with low ( < 1%) or undetectable PD-L1 expression, the anti-PD-1/PD-L1 combination with chemotherapy, compared with chemotherapy alone, is associated with significantly improved OS, PFS, and ORR.

scholarly journals Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis

2018 ◽  
Vol 10 ◽  
pp. 175883591878850 ◽  
Author(s):  
Katrin M. Sjoquist ◽  
Sarah J. Lord ◽  
Michael L. Friedlander ◽  
Robert John Simes ◽  
Ian C. Marschner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Surrogate Endpoint ◽  
Controlled Trials ◽  
First Line ◽  
Free Survival ◽  
Randomized Controlled ◽  
The Difference

Background: Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. Methods: In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Results: Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest ( r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2 = 0.66; platinum/paclitaxel, r2 = 0.44; triplet combinations, r2 = 0.22; biologicals, r2 = 0.30. The median PPS increased over time for the experimental ( Ptrend = 0.03) and control arms ( Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS ( r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger ( r2 = 0.64) than where the median PPS was longer ( r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies.

Meta-Analysis of Single-Agent Chemotherapy Compared With Combination Chemotherapy As Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer

2009 ◽  
Vol 27 (11) ◽  
pp. 1836-1843 ◽  
Author(s):  
Massimo Di Maio ◽  
Paolo Chiodini ◽  
Vassilis Georgoulias ◽  
Dora Hatzidaki ◽  
Koji Takeda ◽  
...  
Keyword(s):  
Randomized Trials ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Grade 3 ◽  
Doublet Chemotherapy

Purpose Doublet chemotherapy is more effective than single-agent as first-line treatment of advanced non–small-cell lung cancer (NSCLC). As second-line treatment, several randomized trials have been performed comparing single-agent with doublet chemotherapy, but each trial had an insufficient power to detect potentially relevant differences in survival. Methods We performed meta-analysis of individual patient data from randomized trials, both published and unpublished, comparing single-agent with doublet chemotherapy as second-line treatment of advanced NSCLC. Primary end point was overall survival (OS). All statistical analyses were stratified by trial. Results Eight eligible trials were identified. Data of two trials were not available, and data of six trials (847 patients) were collected. Median age was 61 years. Performance status was 0 or 1 in 90%; 80% of patients had received previous platin-based chemotherapy. OS was not significantly different between arms (P = .32). Median OS was 37.3 and 34.7 weeks in the doublet and single-agent arms, respectively. Hazard ratio (HR) was 0.92 (95% CI, 0.79 to 1.08). Response rate was 15.1% with doublet and 7.3% with single-agent (P = .0004). Median progression-free survival was 14 weeks for doublet and 11.7 weeks for single agent (P = .0009; HR, 0.79; 95% CI, 0.68 to 0.91). There was no significant heterogeneity among trials for the three efficacy outcomes. Patients treated with doublet chemotherapy had significantly more grade 3 to 4 hematologic (41% v 25%; P < .0001) and grade 3 to 4 nonhematologic toxicity (28% v 22%; P = .034). Conclusion Doublet chemotherapy as second-line treatment of advanced NSCLC significantly increases response rate and progression-free survival, but is more toxic and does not improve overall survival compared to single-agent.

Cetuximab (C225) in the first-line treatment of advanced colorectal cancer (CRC) patients (Pts) with K-ras wild-type (WT) tumors: Does the choice and schedule of fluoropyrimidine (Fp) matter?

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 576-576
Author(s):  
Geoffrey Yuyat Ku ◽  
Benjamin Haaland ◽  
Gilberto de Lima Lopes
Keyword(s):  
Advanced Colorectal Cancer ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
Free Survival ◽  
Epidermal Growth ◽  
First Line Treatment

576 Background: C225, a monoclonal antibody against the epidermal growth factor receptor, has been shown to inconsistently improve response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced CRC Pts with K-ras WT tumors. Methods: We performed a meta-analysis of four trials where K-ras WT Pts received a Fp (capecitabine (C) or bolus (b) or infusional (CI) 5-fluorouracil (5-FU)) and oxaliplatin (oxali) or irinotecan (CPT) ± C225 (CRYSTAL, OPUS, COIN and NORDIC VII trials) and one trial, where K-ras WT and mutant Pts received C225 with capecitabine (C) and oxali or CPT (AIO study). We sought to determine if the choice of Fp affects the response to C225. A mixed effects model similar to that of DerSimonian and Laird was fit by restricted maximum likelihood and used to obtain an overall estimate of the effect of C225 in the presence of CI 5-FU, an indirect estimate of the decrease in the effect of C225 in the presence of C/b5-FU relative to CI 5-FU, and an estimate of the study-to-study variability. Results: Only Pts treated with CI 5-FU based chemo derived benefit from C225. Relative to CI 5-FU, Pts treated with C or b5-FU based doublet chemo had a decrease in RR, PFS and OS. The choice of oxali or CPT did not affect responses to C225. Conclusions: The lack of benefit for C225 with C or b5-FU chemo is unexpected. A possible explanation is increased toxicity with C225, which led to dose reduction of C only in the C225-arm of the COIN study; however, increased toxicity was not seen in the NORDIC VII study. Pending further study, only CI 5-FU regimens should be used with C225. [Table: see text]

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

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