65P - Correlation of overall survival and surrogate endpoints in advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A trial-level analysis

Background

Immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, have radically changed treatment of patients with non-small cell lung cancer (NSCLC). We investigated whether progression-free survival (PFS) and objective response rate (ORR) correlate with overall survival (OS) in phase III randomized controlled trials (RCTs) testing ICIs in advanced NSCLC.

Methods

We systematically reviewed literature to select articles of RCTs investigating ICIs in advanced NSCLC, published by December 2022. For each RCT, we collected data about ORR, hazard ratio of OS (HR_OS) and PFS (HR_PFS). When not reported, odds ratio for ORR (OR_ORR) was manually calculated. Spearman's rank correlation coefficient (ρ) was used to evaluate the relationship between: i) HR_OS and HR_PFS; ii) HR_OS and OR_ORR. Absolute value of ρ indicated the power of correlation between the two variables (0.9–1.0 very strong, 0.7-<0.9 strong, 0.5-<0.7 moderate, 0.3-<0.5 weak, 0-<0.3 negligible).

Results

We identified 25 RCTs with 2 distinct arms and 5 trials with >2 experimental arms. Overall, 36 experimental arms of ICIs ± chemotherapy (ChT), versus standard ChT, were considered for further investigation. Analysis of trials results revealed a weak positive correlation between HR_OS-HR_PFS (n = 35, ρ = 0.4562, p = .0059) and a moderate negative correlation between HR_OS-OR_ORR (n = 36, ρ = -0.6029, p < .001). HR_OS-HR_PFS had a moderate positive relationship in studies testing ICIs in first-line setting (n = 27, ρ = 0.5681, p = .002), as well as in RCTs testing ICIs alone (n = 18, ρ = 0.5498, p = .018). Next, HR_OS-OR_ORR showed only a weak negative relationship in RCTs of ICIs alone (n = 18, ρ = -0.4694 p = .049). Finally, we found that PFS and ORR strongly correlated to OS in trials testing ICIs combined with ChT (n = 17, HR_OS-HR_PFS ρ = 0.7606, p < .001; n = 18, HR_OS-OR_ORRρ = -0.8388, p < .001).

Conclusions

Across trials investigating ICIs in advanced NSCLC, PFS and ORR demonstrated plausible relationship with OS, particularly in RCTs testing combination of ICIs+ChT. However, our results show that caution should be taken when novel treatments are approved based on surrogate outcomes.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Formisano: Financial Interests, Personal and Institutional, Research Grant: AIRC. R. Bianco: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Eli Lilly, Roche, Novartis; Financial Interests, Personal and Institutional, Research Grant: AIRC. A. Servetto: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: AIRC. All other authors have declared no conflicts of interest.