127P - Waning effect of adjuvant EGFR TKIs in resected EGFR-mutated (EGFR-m) NSCLC: A systematic review and meta-analysis of randomized clinical trials (RCTs)

Background

Osimertinib has been approved as adjuvant (adj) therapy in resected EGFR-m non-small cell lung cancer (NSCLC) based on results of the ADAURA trial. Despite the improvement in both disease-free survival (DFS) and overall survival (OS), it is still unclear if adj TKI result in a delay of recurrence rather than cure.

Methods

RCTs comparing TKI versus (vs) placebo (PBO) or platinum-based chemotherapy (CT) as adj treatments in patients (pts) with resected EGFR-m NSCLC were searched in PubMed, EMBASE and Cochrane until 12/2023. Drug-on and drug-off time: defined as time of administration and first year (yr) from the planned end of TKI, respectively. RCTs providing both hazard-ratio (HR) for DFS and/or OS and number of pts free of relapse/death within the drug-on and drug-off time were eligible. Primary endpoints: DFS and OS in TKI both vs PBO and vs CT, reported as HR. Secondary endpoint: risk of relapse/death within the drug-on and drug-off time, estimated by RR.

Results

8 RCTs (n=2352) were included. Treatment with TKI improved both OS (HR 0.53, 95% CI 0.38-0.76, P = 0.0005) and DFS (HR 0.33, 95% CI 0.27-0.40, P < 0.00001) vs PBO. DFS was significantly improved with TKI vs CT (HR 0.54, 95% CI 0.35-0.83, P = 0.005) while there was no effect on OS (HR 0.79, 95% CI 0.52-1.18, P = 0.25). Both for TKI vs PBO (RR 0.50, 95% CI 0.20-0.85, P = 0.01) and TKI vs CT (RR 0.65, 95% CI 0.51-0.84, P = 0.001) the risk of relapse/death favored TKI during drug-on time. However, during the drug off time the risk of relapse/death within the TKI drug-off time did not differ with TKI compared to PBO (RR 1.10, 95% CI 0.82-1.47, P = 0.54) or to CT (RR 1.24, 95% CI 0.87-1.77, P = 0.24).

Table: 127P

Characteristics of included studies

Conclusions

In pts with EGFR-m NSCLC, adj TKI significantly improved DFS compared to PBO and CT. Risk of relapse/death was significantly decreased in the drug-on time with TKI, but no longer within the drug-off time suggesting a waning effect due to TKI withdrawal and the need of continuing therapy to get a long-term benefit.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Imbimbo: Non-Financial Interests, Personal, Principal Investigator: BMS, MedImmune; Non-Financial Interests, Personal, Other, Independent Safety Data Monitoring board member: Immatics. G. Viscardi: Non-Financial Interests, Personal, Training: Sanofi. R. Ferrara: Financial Interests, Personal, Advisory Board, In April 2022: MSD; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Institutional, Invited Speaker: MSD, Pfizer, AstraZeneca, Roche, Sanofi, Novartis, BMS, Ipsen, Daiichi Sankyo Company. All other authors have declared no conflicts of interest.