18 F-BMS-986229 PET to Assess Programmed-Death Ligand 1 Status in Gastroesophageal Cancer

• Published in: Journal of Nuclear Medicine Vol. 65; no. 5; pp. 722 - 727
• Main Authors: Cytryn, Samuel L., Pandit-Taskar, Neeta, Lumish, Melissa A., Maron, Steven B., Gu, Ping, Ku, Geoffrey Y., Chou, Joanne F., Capanu, Marinela, Antoine, Ariel, Loegel, Diane, Feder, Lara, Philemond, Steven, Lyashchenko, Serge K., Lewis, Jason S., Paroder, Viktoriya, Srivastava, Amitabh, Tang, Laura H., Schoder, Heiko, Janjigian, Yelena Y.
• Format: Journal Article
• Language: English
• Published: United States 01.05.2024
• Subjects: Adult; Aged; B7-H1 Antigen - metabolism; Esophageal Neoplasms - diagnostic imaging; Esophageal Neoplasms - metabolism; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Pilot Projects; Positron Emission Tomography Computed Tomography; Prospective Studies; Stomach Neoplasms - diagnostic imaging; Stomach Neoplasms - metabolism; PD-L1 PET; gastric adenocarcinoma; esophageal adenocarcinoma; PD-L1 heterogeneity; immunotherapy
• ISSN: 0161-5505; 2159-662X; 1535-5667
• DOI: 10.2967/jnumed.123.267186

Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient's disease course, and repeated biopsies are invasive and not always feasible. This was a prospective pilot study of the PD-L1-targeting radiotracer, F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the F-BMS-986229 radiotracer intravenously at a dose of 370 MBq over 1-2 min and underwent whole-body PET/CT imaging 60 min later. The primary objective of this study was to evaluate the safety and feasibility of F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Between February 3, 2020, and February 2, 2022, 10 patients with gastroesophageal adenocarcinoma underwent PD-L1 PET. There were no adverse events associated with the F-BMS-986229 tracer, and imaging did not result in treatment delays; the primary endpoint was achieved. Radiographic evaluation of PD-L1 expression was concordant with pathologic assessment in 88% of biopsied lesions, and F-BMS-986229 uptake on PET imaging correlated with pathologic evaluation by the combined positive score (Spearman rank correlation coefficient, 0.64). Seventy-one percent of patients with F-BMS-986229 accumulation on PET imaging also had lesions without F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.