Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer

Stroh, Mark; Green, Michelle; Cha, Edward; Zhang, Nancy R.; Wada, Russ; Jin, Jin

doi:10.1007/s00280-015-2957-7

Cited by 7 publications

(6 citation statements)

References 31 publications

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“…If fewer than 20% of the covariate values were missing, missing covariates were imputed first based on the most similar study with a non-missing value and as the median for continuous variables or the mode for categorical variables across the remaining studies. 30 The fit of the meta-regression model was required to meet the following criteria. First, the regression coefficients of the exposure and covariates should be statistically significant (p < 0.05) and the confidence interval of the coefficients cannot range across 0.…”

Section: Discussionmentioning

confidence: 99%

“…At last, an additive form of binominal effect of therapy line and combination with chemo or target therapy was chosen for the final model in the same way for both any grade and grade greater than or equal to 3 irAEs.

\begin{matrix} left Logit ()(, \Pr_{Any grade irAE}) goodbreak= β_{0} goodbreak+ β_{1} {Factor}_{PD - normalL 1} goodbreak+ β_{2} C_{CTLA - 4} \\ left goodbreak+ β_{3} ()(, line 2 goodbreak+) goodbreak+ β_{4} chemo / target \end{matrix}

\begin{matrix} left Logit ()(, \Pr_{Grade \geq 3 irAE}) goodbreak= β_{0} goodbreak+ β_{1} {Factor}_{PD - normalL 1} goodbreak+ β_{2} C_{CTLA - 4} \\ left goodbreak+ β_{3} {Factor}_{PD - 1} C_{CTLA - 4} \\ left goodbreak+ β_{4} {Factor}_{PD - normalL 1} {Factor}_{CTLA - 4} \\ left goodbreak+ β_{5} ()(, line 2 goodbreak+) goodbreak+ β_{6} chemo / target \end{matrix}

If fewer than 20% of the covariate values were missing, missing covariates were imputed first based on the most similar study with a non‐missing value and as the median for continuous variables or the mode for categorical variables across the remaining studies 30 …”

Section: Methodsmentioning

confidence: 99%

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A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC

Zhang

Kong

Chen

et al. 2022

CPT Pharmacom & Syst Pharma

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Immune checkpoint inhibitors (ICIs) have become a vital part of the therapeutic landscape for non-small cell lung cancer (NSCLC) in recent years benefiting from their remarkable efficacy. However, ICIs are associated with potentially lifethreatening immune-related adverse events (irAEs). This study aims to quantify dose dependence and additional influencing factors of both any grade and grade greater than or equal to 3 irAEs in patients with NSCLC treated by ICIs. The triallevel irAE data was collected and pooled from 129 cohorts in 81 clinical studies.A logit-transformed meta-regression model was applied to derive the quantitative relationship of irAE rate and ICI exposure. Programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) inhibitors showed no dose dependence in patients with NSCLC, whereas cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors exhibited a statistically significant dose dependence when used alone or combined with PD-1 or PD-L1 inhibitors. Besides, therapy line and combination of ICIs with chemotherapy or target therapy were significant covariates. Hopefully, the results of this study can improve clinicians' awareness of irAEs and be helpful for clinical decisions during ICI treatment for NSCLC. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?Conventional clinical trials and meta-analysis have pooled and compared the incidence of immune-related adverse events (irAEs) induced by diverse immune checkpoint inhibitors (ICIs) in several cancer types. WHAT QUESTION DID THIS STUDY ADDRESS?A latest comprehensive model-based meta-analysis based on multiple types of clinical studies was conducted to quantify dose dependence and additional influencing factors of both any grade and grade greater than or equal to 3 irAEs during ICI treatment for non-small cell lung cancer (NSCLC) up to April 30, 2021.

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Section: Discussionmentioning

confidence: 99%

\begin{matrix} left Logit ()(, \Pr_{Any grade irAE}) goodbreak= β_{0} goodbreak+ β_{1} {Factor}_{PD - normalL 1} goodbreak+ β_{2} C_{CTLA - 4} \\ left goodbreak+ β_{3} ()(, line 2 goodbreak+) goodbreak+ β_{4} chemo / target \end{matrix}

\begin{matrix} left Logit ()(, \Pr_{Grade \geq 3 irAE}) goodbreak= β_{0} goodbreak+ β_{1} {Factor}_{PD - normalL 1} goodbreak+ β_{2} C_{CTLA - 4} \\ left goodbreak+ β_{3} {Factor}_{PD - 1} C_{CTLA - 4} \\ left goodbreak+ β_{4} {Factor}_{PD - normalL 1} {Factor}_{CTLA - 4} \\ left goodbreak+ β_{5} ()(, line 2 goodbreak+) goodbreak+ β_{6} chemo / target \end{matrix}

Section: Methodsmentioning

confidence: 99%

A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC

Zhang

Kong

Chen

et al. 2022

CPT Pharmacom & Syst Pharma

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“…As these trials were conducted over almost two decades, it also allowed us to investigate trends in treatment outcomes. Several meta-analyses of second-line therapies in advanced NSCLC have previously been published to estimate the comparative effectiveness and safety of the various therapeutic options [19][20][21][22] and assessed for predictive [20,21] and prognostic factors [22]. To the best of our knowledge, this is the first study focusing on heterogeneity in treatment outcome from the same docetaxel monotherapy as second-line therapy in advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Benchmarking single-arm studies against historical controls from non-small cell lung cancer trials – an empirical analysis of bias

et al. 2019

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Background: Recent trials of novel agents in 'rare' molecular subtypes of non-small cell lung cancer (NSCLC) have used single-arm trial designs and benchmarked outcomes against historical controls. We assessed the consistency of historical control outcomes using docetaxel data from published NSCLC randomized controlled trials (RCTs). Material and methods: Advanced NSCLC RCTs including a docetaxel monotherapy arm were included. Heterogeneity in tumor objective response rates (ORRs), progression-free survival (PFS) and overall survival (OS), and correlations between outcomes and year of trial commencement were assessed. Results: Among 63 trials (N ¼ 10,633) conducted between 2000 and 2017, ORR ranged from 0% to 26% (I 2 ¼ 76.1%, p heterogeneity < .0001). Mean of the median PFS was 3.0 months (range: 1.4-6.4), 3month PFS ranged from 25% to 85% (I 2 ¼ 86.0%, p heterogeneity < .0001). Mean of the median OS was 9.1 months (range: 4.7-22.9), 9-month OS ranged from 23% to 79% (I 2 ¼ 83.0%, p heterogeneity < .0001). Each later year of trial commencement was associated with 0.3% (p ¼ .046), 0.5% (p ¼ .11) and 0.9% (p ¼ .001) improvement in ORR, 3-month PFS and 9-month OS rates, respectively. Conclusions: There was significant heterogeneity and an improving trend in docetaxel outcomes across trials conducted over 20 years. Benchmarking biomarker-targeted agents against historical controls may not be a valid approach to replace RCTs. Innovative study designs involving a concurrent control arm should be considered.

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“…However, meta-analysis strategies developed to handle variability across uncontrolled studies in other indications such as oncology could be used here. [26][27][28] Randomized controlled studies provide statistical control of variability between trials and can strengthen the assessment of treatment and risk factors. However, observational or cohort studies in a real-world setting may be more relevant, and using MBMA of a large and heterogeneous data set of clinical outcome data to evaluate correlations between endpoints could be more informative.…”

Section: Severalmentioning

confidence: 99%

“…With such variability between trials, it would be impossible to explicitly identify the effect of an intervention within one study. However, meta‐analysis strategies developed to handle variability across uncontrolled studies in other indications such as oncology could be used here 26–28 . Randomized controlled studies provide statistical control of variability between trials and can strengthen the assessment of treatment and risk factors.…”

Section: Model‐informed Drug Repurposingmentioning

confidence: 99%

Model‐informed drug repurposing: A pharmacometric approach to novel pathogen preparedness, response and retrospection

Dodds

Xiong

Mouksassi

et al. 2021

Brit J Clinical Pharma

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Funding information Bill and Melinda Gates Foundation During a pandemic caused by a novel pathogen (NP), drug repurposing offers the potential of a rapid treatment response via a repurposed drug (RD) while more targeted treatments are developed. Five steps of model-informed drug repurposing (MIDR) are discussed: (i) utilize RD product label and in vitro NP data to determine initial proof of potential, (ii) optimize potential posology using clinical pharmacokinetics (PK) considering both efficacy and safety, (iii) link events in the viral life cycle to RD PK, (iv) link RD PK to clinical and virologic outcomes, and optimize clinical trial design, and (v) assess RD treatment effects from trials using model-based metaanalysis. Activities which fall under these five steps are categorized into three stages: what can be accomplished prior to an NP emergence (preparatory stage), during the NP pandemic (responsive stage) and once the crisis has subsided (retrospective stage). MIDR allows for extraction of a greater amount of information from emerging data and integration of disparate data into actionable insight.

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Meta-analysis of published efficacy and safety data for docetaxel in second-line treatment of patients with advanced non-small-cell lung cancer

Abstract: This current MBMA identified docetaxel dose-response relationships for both neutropenia and ORR, an effect of age on ORR, and Japanese study effects on both neutropenia and OS.

Cited by 7 publications

References 31 publications

A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC

A model‐based meta‐analysis of immune‐related adverse events during immune checkpoint inhibitors treatment for NSCLC

Benchmarking single-arm studies against historical controls from non-small cell lung cancer trials – an empirical analysis of bias

Model‐informed drug repurposing: A pharmacometric approach to novel pathogen preparedness, response and retrospection

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