1797P - Association between baseline PD-L1 expression in circulating leukocytes, the presence of immune-related adverse events (irAEs) and survival outcomes in patients with extensive-stage small-cell lung cancer (ES-SCLC) from the CANTABRICO trial

Background

Prognosis of patients (p) with ES-SCLC treated with first-line anti-PD-L1 plus platinum-etoposide is poor for most p, only small subset of p achieve long-term benefit. Tumor PD-L1 expression does not predict outcomes with anti-PD-L1 plus platinum- etoposide. We hypothesized that pretreatment PD-L1 expression in circulating immune cells may predict the appearance of irAEs and survival.

Methods

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

Results

The median age was 64 years (48-84), 27p (65.9%) were male, 11p (26.8%) had an ECOG PS of 0 and 30p (73.2%) had an ECOG PS of 1. 13p (31.7%) had liver metastases and 4p (9.8%) had brain metastases. With a median follow-up of 10.2 months (m), the median OS and PFS were 10.3m (95% CI 8.7-11.8) and 7.0m (95% CI 6.0-8.1), respectively. 16p (39%) experienced any grade (G) irAE; 4p (9.8%) >= G3 irAE and 1p (2.4%) G5 irAE. Higher percentages of PD-L1+ monocytes (CD14+) in ES-SCLC p correlated with OS (Spearman correlation: R=0.368, p=0.01) and PFS (R=0.506, p<0.01), and higher percentages of PD-L1+ natural killer cells with PFS (R=0.331, p=0.03). No significant correlation was observed between percentages of PD-L1+ CD4+/CD8+/CD20+ lymphocytes, or PD-L1+ neutrophils and survival. Significant correlation with the development of irAEs were observed only with higher percentages of PD-L1+ neutrophils (p=0.003).

Conclusions

These findings indicate the potential of PD-L1 expression in neutrophils and monocytes as non-invasive predictive biomarkers for irAEs and survival in ES-SCLC treated with durvalumab plus platinum-etoposide.

Clinical trial identification

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

Editorial acknowledgement

Legal entity responsible for the study

AstraZeneca Farmacéutica Spain.

Funding

AstraZeneca Farmacéutica Spain.

Disclosure

A. Barba Joaquín: Financial Interests, Personal, Invited Speaker: Pfizer, MSD, Sanofi, BMS, Novartis, Roche, AstraZeneca, Pierre Fabre; Financial Interests, Personal, Advisory Board: BMS, Sanofi; Non-Financial Interests, Principal Investigator, PI - Clinical Trial C4221016: Pfizer. 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: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Johnson & Johnson, MSD, Amgen, Pfizer. E. Arriola Aperribay: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Guardant Health, MSD, Pfizer, Takeda, Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Lilly, Roche; Other, Personal, Other, Co-founder: Trialing Health; Non-Financial Interests, Institutional, Research Grant: AstraZeneca. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. P. Diz Tain: Financial Interests, Personal, Invited Speaker: BMS, Boehringer Ingelheim, MSD, Takeda, Pfizer, Amgen; Financial Interests, Personal, Advisory Role: BMS, Boehringer Ingelheim, MSD, Takeda; Financial Interests, Personal, Training: BMS, Boehringer Ingelheim, MSD, Takeda; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Roche; Financial Interests, Personal and Institutional, Training: AstraZeneca, Roche; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Roche; Financial Interests, Institutional, Training: Pfizer; Financial Interests, Institutional, Principal Investigator: Mirati. A.L. Moreno Vega: Financial Interests, Personal, Invited Speaker: PharmaMar, Pfizer, Takeda, Roche. Á. Callejo: Financial Interests, Full or part-time Employment: AstraZeneca. S. Vidal: Financial Interests, Personal, Invited Speaker: UCB, Sanofi, Janssen, AstraZeneca; Financial Interests, Personal, Writing Engagement: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Novartis, Precigen, Almirall, AstraZeneca. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, BMS, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche; Non-Financial Interests, Leadership Role, Board Member: Associacio Contra El Cancer Barcelona. All other authors have declared no conflicts of interest.