P48.20 Trends in Trial Design, Interpretation and Survival in Phase III Clinical Trials on Extensive-Stage SCLC Between 2000 and 2019

Abstract

The improvement in the outcomes of patients with extensive-stage small cell lung cancer (SCLC) has been modest over past decades despite tremendous efforts made in optimising treatment outcomes as demonstrated in multiple trials. This review aims to investigate the trends in trial design, interpretation and magnitude of survival benefit described in phase III randomized controlled trials (RCTs) evaluating first-line systemic antineoplastic therapy in patients with extensive-stage SCLC over past two decades. We searched biomedical database for relevant trials published between 2000 and 2019. Descriptive statistics were used to summarize the patterns in trial design and interpretation for each time period (2000-2004, 2005-2009, 2010-2014 and 2015-2019). The Cochran-Armitage trend test was performed to test the changes over time in reporting the primary end point, quality of life (QoL) and trial interpretations. The F test was used to test the change over time in the trial sample size and the reported net survival benefit. The net survival benefit was defined as the difference in median survival time between experimental and control arms. Thirty-eight eligible trials were identified, involving 11,689 patients with 76 treatment arms. Overall survival (OS) was the most common primary end point of trials over the time periods (89% in 2000-2004; 87% in 2005-2009; 80% in 2010-2014; 78% in 2015-2019; P= 0.99). There was a trend toward fewer number of trials that included QoL outcomes (44% in 2000-2004; 60% in 2005-2009; 40% in 2010-2014; 11% in 2015-2019; P= 0.31). Out of the sixteen (42.1%) trials that reported positive conclusions, only seven (18.4%) trials met their primary endpoint; these observations remained stable over time (positive trial conclusion: P= 0.99; trials met their primary endpoint: P= 0.53). The trial sample sizes were increasing over time (median sample size: 154 in 2000-2004; 220 in 2005-2009; 370 in 2010-2014; 299 in 2015-2019; P= 0.08). A trend toward increasing magnitude of survival gain in positive trials was seen over time (1.1 months in 2000-2004; 0.65 months in 2005-2009; 1.6 months in 2010-2014; 2.0 months in 2015-2019; P= 0.92). There was no significant shift in the design, interpretation and survival outcomes of phase III randomized controlled trials of systemic antineoplastic therapy in extensive-stage small cell lung cancer over the past two decades. The use of quality of life outcomes is declining while the improvement in the magnitude of overall survival benefit is modest. More effective systemic agents are needed to improve both the survival and quality of life outcomes of these patients.