Abstract 1559P
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.
Resources from the same session
1521P - Addition of durvalumab to CROSS in oesophageal adenocarcinoma is feasible and safe
Presenter: Hans Schloesser
Session: Poster session 21
1523P - Phase II dose optimization results from MOUNTAINEER-02: A study of tucatinib, trastuzumab, ramucirumab, and paclitaxel for HER2+ gastroesophageal cancer (GEC)
Presenter: Mustapha Tehfe
Session: Poster session 21
1524P - First-line TST001 plus capecitabine and oxaliplatin (CAPOX) for advanced G/GEJ cancer with CLDN18.2 positive overall survival data from study transtar102-Cohort C
Presenter: Lin Shen
Session: Poster session 21
1526P - Phase Ib results of bemarituzumab (BEMA)+mfolfox6+nivolumab (NIVO) for advanced gastric/gastroesophageal junction cancer (G/GEJC): Fortitude-102 part 1
Presenter: Zev Wainberg
Session: Poster session 21
1527P - Efficacy and safety of infigratinib in locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients with FGFR2 gene amplification
Presenter: Jiajia Yuan
Session: Poster session 21
1528P - A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors
Presenter: Daniel Olson
Session: Poster session 21
1529P - Tislelizumab plus chemotherapy sequential neo-chemoradiotherapy therapy as total neoadjuvant therapy in locally advanced esophageal squamous cell carcinoma (ETNT)
Presenter: Wenwu He
Session: Poster session 21
1530P - Health-related quality of life (hrqol) in patients with claudin-18 isoform 2-positive (CLDN18.2+) locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mg/GEJ) adenocarcinoma: Results from SPOTLIGHT and GLOW
Presenter: Florian Lordick
Session: Poster session 21