Background and importance Numerous randomised controlled trials (RCT) have been conducted over recent decades to identify the optimal therapeutic option for patients with advanced non-small cell lung cancer (NSCLC). However, only modest clinical benefits have been achieved.
Aim and objectives To analyse primary efficacy outcomes reported and the design of phase III RCT of advanced NSCLC published in 2018.
Material and methods A structured search using MEDLINE and EMBASE was conducted for phase III RCT reported in 2018 for treating advanced NSCLC. Any English written study comparing at least two systemic agents was included. Selected trials were scrutinised to identify potential duplications. The following information was recorded: sample size, treatment line, pharmacological agents, intention to treat (ITT) analysis, ESMO magnitude of clinical benefit scale (MCBS) V1.1, and assessment of quality of life (QoL) and primary efficacy outcomes (overall survival (OS) or progression free survival (PFS)), along with the investigators’ conclusions on the experimental arm (positive or negative result).
Results Fourteen studies were selected from 134 search results, showing a median sample size of 464 patients (IQR 276–611). Eight trials (57.1%) evaluated a firstline treatment for advanced NSCLC. The pharmacological agents were distributed as follows: EGFR inhibitors (n=3); ALK inhibitors (n=3); anti-PD-L1 (n=3); and other (n=5); 57% had already been approved for treating advanced NSCLC. All RCT evaluated the efficacy outcomes in the ITT population. ESMO MCBS estimation was applicable to 8 (57%) studies showing: grade 4 (n=3: alectinib, crizotinib and osimertinib), grade 3 (n=2: osimertinib and pembrolizumab based regimen) and grade 2 (n=3: anlotinib, dulanermin based scheme and atezolizumab based regimen). PFS was the primary outcome in 10/14 (71.4%) RCT and the co-primary outcome with OS in 3 of these trials. OS was the primary outcome in 4/14 (28.6%) RCT and QoL was assessed in 5/14 (35.7%) trials, with just one trial reporting a significant improvement. Conclusions were positive in 9/14 (64.3%) RCT.
Conclusion and relevance QoL, which has been found to be a strong predictor of survival and toxicity outcomes, was evaluated in only 35.7% of the selected trials. It was also disturbing that only 50% of the trials considered OS as the primary/co-primary efficacy outcome. However, the results seemed to be positive in 64.3% of trials.
References and/or acknowledgements University of Granada
No conflict of interest.