Abstract 943P
Background
Overall survival (OS) is the gold standard for assessing treatment efficacy in non-small-cell lung cancer (NSCLC) but can take many years to sufficiently mature in trials of resectable NSCLC. Event-free survival (EFS) is an accepted endpoint for neoadjuvant therapy (NAT) and can be a surrogate for OS. This systematic literature review and meta-analysis investigated the statistical association between EFS and OS in patients with NSCLC receiving NAT.
Methods
Systematic searches identified sources reporting both EFS and OS data in patients with resectable stage I–IIIB NSCLC receiving NAT, including chemotherapy and/or immunotherapy (IT). Electronic searches were ran in July 2021 in Embase, MEDLINE® and the Cochrane Library and covered 2000–2021. Three congresses covering 2018–2021 were searched. Extracted outcomes included hazard ratios (HRs) comparing EFS and OS between treatment arms, median EFS (mEFS) and OS (mOS). Correlation and regression analyses were conducted to evaluate the association between mEFS and mOS, and the effect of treatment on EFS and OS using log HRs. The analyses excluded sources that only included patients with epidermal growth factor receptor mutations.
Results
We identified 74 sources, of which 18 reported randomized controlled trials (RCTs), 26 reported single-arm studies and 30 reported observational studies. Of the 74 sources, 39 reported both mEFS and mOS, and 8 reported HRs from RCTs. None included IT. Analysis of median values found a positive linear correlation between mEFS and mOS (weighted Pearson’s correlation coefficient r = 0.819; 95% confidence interval [CI] 0.728–0.922; p < 0.05). The longest mEFS and mOS were from NAT arms that also included adjuvant therapy. Analysis of treatment effects from RCTs found a positive linear correlation between EFS and OS log HRs (weighted r = 0.864; 95% CI 0.809–0.992; p < 0.05), and a strong association between log treatment effects (random-effects meta-regression, R 2 = 0.777).
Conclusions
We found a strong association between EFS and OS, indicating that improvements in EFS are likely to be predictive of improvements in OS. EFS may therefore be a reliable surrogate for OS after NAT in resectable NSCLC.
Clinical trial identification
Editorial acknowledgement
The authors thank Erica Boschin and Helen Schofield at Oxford PharmaGenesis, Oxford, UK, for medical writing support.
Legal entity responsible for the study
The authors.
Funding
The study was funded by AstraZeneca, Cambridge, UK.
Disclosure
M. Berktas, P. Chander, I. Diaz Perez, N.E. Georgoulia, R. Hettle, P. Morten: Financial Interests, Personal and Institutional, Full or part-time Employment: AstraZeneca. A. Couto: Other, Institutional, Writing Engagements: Oxford PharmaGenesis. C. Eichinger: Financial Interests, Personal and Institutional, Writing Engagements: Oxford PharmaGenesis. P. Field: Financial Interests, Institutional, Writing Engagements: Oxford PharmaGenesis. All other authors have declared no conflicts of interest.