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

Abstract

Background: A 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.

Methods: Phase 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.

Results: A 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.

Conclusions: Despite Consolidated Standards of Reporting Trials guidelines, allocation method has rarely been reported. The choice of stratification factor remains inconsistent across studies.

Keywords: First‐line; non‐small cell lung cancer; phase III.

Figure 1

Differences in primary endpoint by decades and regions. Studies that were conducted in multiple continents were defined as international. Most studies in the 1980s did not report a primary endpoint. There was no international study in the 1980s. AEs, adverse events; EU, European Union; ORR, overall response rate; OS, overall survival; PFS, progression‐free survival; QoL, quality of life; TTP, time to progression. Clinical benefit, ; AEs, ; QoL, ; unclear, ; multiple, ; PFS/TTP, ; ORR, ; OS, .