Systematic analysis of design and stratification for phase III trials in first‐line advanced non‐small cell lung cancer

Abstract

BackgroundA recent study reviewed phase III trials of first‐line advanced non‐small cell lung cancer (NSCLC) conducted from 1981 to 2010, and provided trends in the study outcome. However, such trials have never been analyzed in detail for design and stratification factors.MethodsPhase III studies of systemic treatment for first‐line advanced or metastatic NSCLC published in English literature between 1981 and 2010 were identified. Characteristics, including sample size, number of trials, region, rate of meeting accrual goal, primary endpoint, type of phase III, interim analysis, allocation method, and stratification factors, were determined for each decade.ResultsA total of 162 studies met the criteria. The number of studies and sample size increased over the three decades. The primary endpoint was reported more frequently in recent decades, and non‐overall survival endpoints were chosen in European and Asian studies. Interim analysis was conducted more commonly during the 2000s. Allocation method was rarely reported throughout the three decades. The number of stratification factors increased significantly from one in 1980s to three in 2000s. Performance status, stage, and institution were most frequently selected, and at least one of the three factors was used in most of the studies in the 2000s. However, there are many other stratification factors that were used infrequently.ConclusionsDespite Consolidated Standards of Reporting Trials guidelines, allocation method has rarely been reported. The choice of stratification factor remains inconsistent across studies.

YAP and TAZ in Lung Cancer: Oncogenic Role and Clinical Targeting

“…Promising results have been obtained with EGFR inhibitors, which after several randomized phase 3 trials have been approved as first-line treatment in advanced NSCLC patients positive for EGFR mutations, showing higher progression-free survival and lower toxicity when compared to standard chemotherapy [ 181 ]. However, in Western populations, only 20% of patients with metastatic lung adenocarcinoma can be stratified for treatment with current targeted therapies with median responses of approximately a year [ 182 , 183 ]; thus, cytotoxic chemotherapy remains the elected therapy for first-line treatment of advanced disease. Often, the emergence of resistance to chemotherapy, radiotherapy, or targeted therapies reduces their efficacy after an initial response [ 184 , 185 , 186 ].…”

Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer

“…To adjust for potential variability between patients, the models included common stratification factors of ECOG PS (0 or 1 vs 2 in the pooled analysis and individual studies), presence of brain metastases (yes vs no in the pooled analysis and G1T28‐05) and sensitivity to first‐line treatment (sensitive vs resistant in G1T28‐03) as these stratification factors have previously been shown in SCLC trials to predict treatment outcomes. 33 , 34 , 35 Study (G1T28‐05, G1T28‐02 and G1T28‐03 in the pooled analysis) was also included as a fixed effect in order to adjust for potential variability between studies. The analyses of cumulative incidence of FN, prolonged SN and RBC transfusions included corresponding baseline laboratory values as covariates.…”

“…The treatment effect of trilaciclib compared to placebo was assessed using a negative binomial regression model, adjusting for duration of treatment in weeks or number of cycles. To adjust for potential variability between patients, the models included common stratification factors of ECOG PS (0 or 1 vs 2 in the pooled analysis and individual studies), presence of brain metastases (yes vs no in the pooled analysis and G1T28‐05) and sensitivity to first‐line treatment (sensitive vs resistant in G1T28‐03) as these stratification factors have previously been shown in SCLC trials to predict treatment outcomes 33‐35 . Study (G1T28‐05, G1T28‐02 and G1T28‐03 in the pooled analysis) was also included as a fixed effect in order to adjust for potential variability between studies.…”