1559P - PD-L1 expression as a negative predictive biomarker in advanced esophageal squamous cell cancer treated with chemotherapy alone: A KMSubtraction derived analysis

Background

Prognosis for aESCC (advanced esophageal squamous cell carcinoma) remains poor. Programmed death-ligand 1 (PD-L1) expression is a well-established positive predictive biomarker for response to immunotherapy in aESCC. However, the association between PD-L1 and response to chemotherapy alone remains unclear. This study aims to determine the prognostic significance of PD-L1 expression in patients treated with first-line chemotherapy alone in aESCC.

Methods

First-line phase III randomized trials that included PD-L1 expression as a biomarker in aESCC were extracted after a systematic search of Embase and PubMed from inception until September 24, 2022. Only trials that reported PD-L1 stratified Kaplan-Meier (KM) curves of chemotherapy arms were included. A graphical reconstructive algorithm was used to estimate time-to-event outcomes from reported KM plots in all overall and reported subgroup cohorts. Where unavailable, KMSubtraction was utilized to derive KM plots of unreported PD-L1 subgroups. Thereafter, individual patient data meta-analysis was conducted. Survival analyses for overall and progression-free survival (OS, PFS) were conducted with Cox proportional hazards models with a shared-frailty term incorporated to account for inter-study differences.

Results

Chemotherapy arms from 5 randomized phase III trials - CheckMate-648, ESCORT-first, KEYNOTE-590, RATIONALE306 and ORIENT-15 – comprising 1,517 patients were included in the OS analysis. Compared to PD-L1 low expressing tumors, patients with PD-L1 high expressing tumors were at a significantly higher risk of mortality (PD-L1 high [n=769] vs PD-L1 low [n=748], HR=1.152, 95%-CI: 1.018 – 1.305, p=0.025). Three trials – CheckMate-648, ESCORT-first and ORIENT-15 – comprising 949 patients treated with chemotherapy alone were included in the PFS analysis. Likewise, patients with PD-L1 high expressing tumors were at a higher risk of tumor progression, although this was not significant (PD-L1-high [n=513] vs PD-L1-low [n=436], HR=1.076, 95%-CI: 0.923 - 1.253, p=0.35).

Conclusions

Our study found PD-L1 expression is a negative predictor of overall survival in aESCC treated with first-line chemotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

R. Sundar: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD, GSK, DKSH, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, BMS, Roche, Taiho, AstraZeneca, DKSH, Ipsen; Financial Interests, Personal and Institutional, Local PI: MSD, Taiho, BMS, Novartis; Financial Interests, Personal, Stocks/Shares: Teladoc; Financial Interests, Institutional, Advisory Board: Paxman Coolers; Non-Financial Interests, Advisory Role: Paxman Coolers; Non-Financial Interests, Principal Investigator: MSD, Natera. All other authors have declared no conflicts of interest.