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
4094 - Treatment outcomes for adult patients with localized osteosarcoma treated with chemotherapy without methotrexate
Presenter: Marília Silva
Session: Poster Display session 1
Resources:
Abstract
3157 - Efficacy and safety of anlotinib in advanced leiomyosarcoma: Subgroup analysis of a phase IIB trial (ALTER0203)
Presenter: Yihebali Chi
Session: Poster Display session 1
Resources:
Abstract
3710 - The effect of treatment line on the efficacy of Anlotinib hydrochloride in advanced alveolar soft part sarcoma patients
Presenter: Zhiwei Fang
Session: Poster Display session 1
Resources:
Abstract
3184 - Prior exposure to pazopanib (PAZ) did not minor efficacy of regorafenib (REG) in non-adipocytic soft tissue sarcoma patients (pts)
Presenter: Nicolas Penel
Session: Poster Display session 1
Resources:
Abstract
798 - Pexidartinib (Pex) for locally advanced tenosynovial giant cell tumor (TGCT): characterization of hepatic adverse reactions (ARs)
Presenter: Sebastian Bauer
Session: Poster Display session 1
Resources:
Abstract
6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult
Presenter: Qiyuan Bao
Session: Poster Display session 1
Resources:
Abstract
5450 - Reversion of resistance to mTOR inhibitors with the addition of exemestane in patients with malignant PEComa.
Presenter: Roberta Sanfilippo
Session: Poster Display session 1
Resources:
Abstract
4279 - Efficacy and Safety of VEGFR2 Inhibitor Apatinib combined with chemotherapy for Sarcoma in Stage IV
Presenter: Zhiwu Ren
Session: Poster Display session 1
Resources:
Abstract
5929 - Outcomes of metastatic soft tissue sarcoma treated with Pazopanib from dedicated medical oncology sarcoma clinic: A holistic care approach from a developing country
Presenter: Akhil Kapoor
Session: Poster Display session 1
Resources:
Abstract
2469 - Inhibition of mTOR signaling enhances Trabectedin activity in Soft Tissue Sarcoma
Presenter: David Moura
Session: Poster Display session 1
Resources:
Abstract