Abstract 3411
Background
Gastrointestinal stromal tumours (GISTs) account for 1% of all primary gastrointestinal cancers. In cancer, suppressive immune checkpoints, including butyrophilin sub-family 3A/CD277 receptors (BTN3A), programmed death protein (PD-1) and its ligand PD-L1, are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. Since recent studies showed that PD-1 and PD-L1 expression in cancer may be an important prognostic factor, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can help predict survival in metastatic GIST patients.
Methods
Using specific homemade ELISA assays not yet commercially available, the plasma PD-1, PD-L1, BTN3A1 and pan-BTN3As levels were analyzed in 20 metastatic GIST patients harbouring c-KIT exon 11 mutations, before starting treatment with 400 mg Imatinib. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Data was generated using the MedCalc software for Windows, version 18.2.1.
Results
Kaplan-Meier survival analysis was used to characterize prognostic relevance of soluble PD-1, PD-L1, BTN3A1 and pan-BTN3As in metastatic GIST patients, suggesting that their plasma levels could serve as survival predictor. For each analyzed biomarker, statistically significant differences in progression free-survival (PFS) between patients with plasma concentrations above and under median values were detected. Plasma level thresholds correlated with shorter survival and poor prognosis were established for PD-1 (>6.89 ng/ml), PD-L1 (>0.74 ng/ml), BTN3A1 (>7.19 ng/ml) and pan-BTN3As (>4.38 ng/ml). Conversely, patients with plasma levels under thresholds showed a median PFS that was approximately 58 months longer than to the previous.
Conclusions
Our study, for the first time, reveals that monitoring the concentration of soluble forms of inhibitory immune checkpoints in plasma can help predict survival in metastatic GIST patients and therefore improve their treatments. We showed that high plasma levels of these immune checkpoints correlate with poor outcome and could be used in future as prognostic factors.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4228 - Clinical Evaluation of Drug-Eluting Bead Transcatheter Arterial Chemoembolization(D-TACE) versus Conventional TACE in Treatment of unresectable Hepatocellular Carcinoma
Presenter: Yi Chen
Session: Poster Display session 1
Resources:
Abstract
3930 - Safety profile of tepotinib in patients with advanced solid tumors: pooled analysis of phase I and II data
Presenter: Thomas Decaens
Session: Poster Display session 1
Resources:
Abstract
5373 - Drug-drug interaction profile of tepotinib with CYP3A and P-gp substrates
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
5455 - Bioavailability of tepotinib: impact of omeprazole and food
Presenter: Juergen Heuer
Session: Poster Display session 1
Resources:
Abstract
2618 - Tislelizumab Exposure-Response Analyses of Efficacy and Safety in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2563 - Population Pharmacokinetics of Tislelizumab in Patients with Advanced Tumors
Presenter: Chi-Yuan Wu
Session: Poster Display session 1
Resources:
Abstract
2021 - The Addition of Metformin to Systemic Anticancer Therapy
Presenter: Jung Han Kim
Session: Poster Display session 1
Resources:
Abstract
5243 - Growth modulation index (GMI) as a comparative measure of clinical activity of larotrectinib versus prior systemic treatments in adult and pediatric TRK fusion cancer patients
Presenter: Antoine Italiano
Session: Poster Display session 1
Resources:
Abstract
598 - Analysis of the overall survival and main surrogates used for FDA approvals in solid and hematological malignancies.
Presenter: Maria Kleniewska-Wieczor
Session: Poster Display session 1
Resources:
Abstract
5381 - Comparison of intratumoral docetaxel exposure in cancer patients between nanoparticle entrapped docetaxel (CPC634) and conventional docetaxel (Cd): the CriTax study
Presenter: Ruben Van Eerden
Session: Poster Display session 1
Resources:
Abstract