Abstract 1235P
Background
A recent study demonstrated a robust correlation between pathologic complete response (pCR) and major pathologic response (MPR) with 2-year event-free survival (EFS) in neoadjuvant immune checkpoint inhibitor (ICI) trials of resectable non-small cell lung cancer (NSCLC). We analysed the impact of PDL1 status and histology on the strength of these associations.
Methods
We searched for randomised controlled trials (RCTs) examining neoadjuvant ICI in early stage NSCLC. Study eligibility criteria were: ≥80 patients, an ICI arm (including combination ICI plus chemotherapy), pCR/MPR and EFS outcomes reported for subgroups categorised by PDL1 status and histology. Using weighted linear regression, correlations between pCR and MPR against 2-year EFS were assessed. For trial level analysis, odds ratio (OR) for pathological responses and hazard ratio (HR) for EFS were assessed. Coefficient of determination (R2) of <0.6 was considered as poor correlation and >0.7 as strong correlation.
Results
We identified five RCTs with a total of 2098 patients available for analysis. In the PDL1≥1% group, correlations between pCR and MPR vs 2-year EFS were strong (R2=0.82 and 0.96 respectively) but moderate in the PDL1<1% group (R2=0.67 and 0.64 respectively). In squamous NSCLC, correlations between pCR and MPR vs 2-year EFS were strong (R2=0.95 and 0.98). In non squamous NSCLC, correlation between pCR and 2-year EFS was weak (R2=0.55) but strong between MPR and 2-year EFS (R2= 0.79). For trial level analysis, correlation between pCR OR and HR EFS was strong in the PDL1<1% group but poor in the PDL1≥1% group (R2= 0.87 vs 0.46 respectively). Correlation was poor for pCR OR and HR EFS in both squamous and nonsquamous NSCLC (R2= 0.02 and 0.54 respectively). Limited observations for MPR and OS precluded these analyses.
Conclusions
There is strong correlation and surrogacy between pCR/MPR and EFS in resectable NSCLC with PDL1≥1%. pCR and MPR were prognostic for 2-year EFS outcomes in PDL1<1% and squamous subgroups but did not demonstrate good surrogacy at the trial level. Similarly pCR was a poor surrogate for EFS in nonsquamous NSCLC. Mature follow-up data will help to further validate pathological response as a surrogate endpoint.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Roche, Janssen, Gilead, MSD, GSK, Norvatis, Merck kGA; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Amgen, Merck kGA, Norvatis, Roche. All other authors have declared no conflicts of interest.
Resources from the same session
1230P - Association between early endpoints and survival outcomes in neoadjuvant treatment of resectable non-small cell lung cancer (NSCLC): A multi-country retrospective study
Presenter: Mariano Provencio Pulla
Session: Poster session 04
1231P - Clinical characteristics and real-world treatment patterns in stage I-III resectable NSCLC: THASSOS-INTL study
Presenter: Kumar Prabhash
Session: Poster session 04
1233P - Genomic scarring score as a criterion for PARP inhibitor administration in early-stage NSCLC
Presenter: Apostolos Klinakis
Session: Poster session 04
1234P - Stage migration in resectable NSCLC
Presenter: Guus Heuvel
Session: Poster session 04
1236P - ctDNA-Lung-Detect: Profiling of non-shedding ctDNA early stage resected non-small cell lung cancers
Presenter: Sam Khan
Session: Poster session 04
1237P - Association of LRRC15 protein expression with 5-year survival in lung adenocarcinoma patients
Presenter: Jessie Woon
Session: Poster session 04
1238TiP - Combining immunotherapy with Trop2 ADc in early stage non-small cell lung cancer (CITADEL)
Presenter: Siu Ching Li
Session: Poster session 04