313P - Baseline PD-L1 expression in circulating neutrophils predicts immune-related adverse events (irAEs) in patients with extensive-stage small-cell lung cancer from CANTABRICO trial

Background

Patients (p) with extensive stage small-cell lung cancer (ES-SCLC) receiving first-line anti-PD-L1 plus platinum-etoposide can present inflammatory side effects commonly known as immune-related adverse events (irAEs) induced by T-cell activation. Their appearance is unpredictable as there is no established predictive biomarker. An early detection could be essential to avoid serious side effects and costs. We hypothesized that pretreatment PD-L1 expression in circulating immune cells could predict their appearance.

Methods

Baseline blood samples from 41p with ES-SCLC enrolled in NCT04712903 CANTABRICO trial (EudraCT 2020-002328-35) were analyzed by flow cytometry. All p received first-line durvalumab plus platinum-etoposide. We determined the percentage of PD-L1+ cells among the leukocyte subpopulations and correlated them with toxicity. Descriptive statistics were used to report baseline characteristics. Kaplan-Meier was used to estimate survivals. T-test was used for comparisons between groups.

Results

The median age was 64 years, 27p (65.9%) were male, 30p (73.2%) had an ECOG PS of 1. With a median follow-up of 10.2 months (m), the median OS and PFS were 10.3 m (95% CI 8.7–11.8) and 7.0 m (95% CI 6.0–8.1). irAEs are summarized in the table. 16p (39%) experienced any grade (G) irAE; 4p (9.8%) ≥ G3 irAE and 1p (2.4%) G5 irAE. Significant correlation with the development of irAES was observed in p with higher percentages of PD-L1+ neutrophils at baseline (p=0.003). No statistically significant correlation was observed between percentages of PD-L1+ CD4+/CD8+/CD20+ lymphocytes, monocytes or natural killer cells and the presence of irAEs.

Description of irAEs

Conclusions

These findings indicate the potential role of PD-L1 expression in neutrophils as a non-invasive predictive biomarker for the appearance of irAEs in ES-SCLC p treated with durvalumab plus platinum-etoposide.

Clinical trial identification

EudraCT 2020-002328-35, Protocol number: D419QC00005.

Legal entity responsible for the study

AstraZeneca Farmacéutica Spain, S.A.

Funding

AstraZeneca Farmacéutica Spain, S.A.

Disclosure

A. Barba Joaquín: Financial Interests, Personal, Invited Speaker: Pfizer, MSD, Sanofi, BMS, Novartis, Roche, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Expert Testimony: BMS; Financial Interests, Personal, Advisory Board: Sanofi, Roche, AstraZeneca; Financial Interests, Personal, Other, congress funding: Janssen, Pfizer, Roche, Pierre Fabre; Non-Financial Interests, Personal, Principal Investigator, PI - Clinical Trial C4221016: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Clinical Trial CA224-1044: BMS; Non-Financial Interests, Personal, Principal Investigator, DZ2022E0005 & DZ2019E0001: Dizal. I.G. Sullivan: Financial Interests, Personal, Advisory Board: Roche, Takeda, Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Takeda. M.D. Isla Casado: Non-Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: AstraZeneca. E. Arriola Aperribay: Financial Interests, Institutional, Research Grant, Grants or contracts: AstraZeneca, BMS; Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, Roche, Takeda, MSD, Pfizer, Janssen, BMS; Financial Interests, Personal, Advisory Board: Lilly, Sanofi; Financial Interests, Institutional, Other, Receipt of equipment, materials, drugs, medical writing, gifts or other services: AstraZeneca. L. Paz-Ares: Financial Interests, Personal, Other, Consulting fees: consultant: Lilly, MSD, Roche, PharmaMar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Regeneron, Gilead, AbbVie, Daiichi Sankyo; Financial Interests, Personal, Other, Grants or contracts: consultant: MSD, AstraZeneca, BMS, Pfizer; Financial Interests, Personal, Other, Honoraria for lectures: AstraZeneca, Janssen, Merck, Mirati, Sanofi. P. Diz Tain: Financial Interests, Personal and Institutional, Invited Speaker: BMS, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Advisory Role: BMS, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Training: BMS, AstraZeneca, Roche; Financial Interests, Personal and Institutional, Principal Investigator: BMS, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, MSD, Takeda, Pfizer, Amgen; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, MSD, Takeda; Financial Interests, Personal, Training: Boehringer Ingelheim, MSD, Takeda, Pfizer. Á. Callejo, J.L. Lechuga Martos, M. Dominguez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca Farmacéutica Spain. S. Vidal: Financial Interests, Personal, Invited Speaker: UCB, Sanofi, Janssen, AstraZeneca, Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Novartis, Precigen, Almirall, AstraZeneca. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Casen Recordati, BMS, Sanofi, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn, Casen Recordati; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche; Non-Financial Interests, Personal, Leadership Role, Board Member: Associacio contra el Cancer Barcelona; Non-Financial Interests, Personal, Leadership Role: Asocacion para la Investigacion del Cancer de Pulmon en Mujeres. All other authors have declared no conflicts of interest.