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

Abstract

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. Methods: This was a prospective pilot study of the PD-L1-targeting radiotracer, ¹⁸F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the ¹⁸F-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 ¹⁸F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Results: 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 ¹⁸F-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 ¹⁸F-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 ¹⁸F-BMS-986229 accumulation on PET imaging also had lesions without ¹⁸F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had ¹⁸F-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. Conclusion: PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.

Keywords: PD-L1 PET; PD-L1 heterogeneity; esophageal adenocarcinoma; gastric adenocarcinoma; immunotherapy.

Graphical abstract

FIGURE 1.

Concordance between PD-L1 PET, PD-L1 CPS, and ¹⁸F-FDG PET. (A) PD-L1 pathologic evaluation by CPS correlated with PD-L1 PET visualization score (r_s = 0.64) and SUV (r_s = 0.61). (B) All 10 patients are plotted according to their maximum PD-L1 PET visualization score. Visualization score of 4 or 5 is considered positive. (C) Among 8 patients with PD-L1 CPS–positive tumors, there were 21 ¹⁸F-FDG–avid lesions, of which 9 were PD-L1 PET–avid. Total numbers of PD-L1 PET–avid lesions and ¹⁸F-FDG PET–avid lesions at each disease site are shown, as well as those that were ¹⁸F-FDG–avid but not PD-L1–avid.

FIGURE 2.

PD-L1 PET without uptake corresponds to PD-L1–negative biopsy. Gastric mass biopsy (top left) demonstrated PD-L1 CPS of 10. Patient was treated with chemotherapy followed by surgery but then developed metastatic recurrence to lymph nodes, biopsy of which demonstrated PD-L1 CPS < 1 (top right). PD-L1 PET (bottom left), corresponding CT (bottom middle), and ¹⁸F-FDG PET (bottom right) obtained at time of recurrence depict non–PD-L1–avid but ¹⁸F-FDG–avid gastrohepatic lymph node (arrows) that was biopsied. Left intensity scale bar corresponds to PD-L1 PET, and right color scale bar corresponds to ¹⁸F-FDG PET. Both are in absolute SUV units.

FIGURE 3.

PD-L1 PET tracer accumulation across multiple lesions and in response to treatment. (A) PD-L1 PET imaging demonstrating tracer accumulation across both adrenal (top left) and vertebral (bottom left) lesions in patient 6, who had primary progression on FOLFOX chemotherapy after 2 mo but durable (10.9 mo) response to pembrolizumab as second-line therapy. Corresponding CT and ¹⁸F-FDG PET scans obtained at same time as PD-L1 PET are shown in middle and right panels, respectively. (B) Patient 8 with locally advanced, unresectable gastroesophageal junction (GEJ) adenocarcinoma had tracer accumulation at primary GEJ mass (left) and was treated with FOLFOX and nivolumab. He had significant tumor regression (right) allowing for surgical resection, received adjuvant 5-fluorouracil (5-FU) and nivolumab, and remained without evidence of disease 21.9 mo later. Left intensity scale bar corresponds to both PD-L1 and ¹⁸F-FDG PET images in Figure 3A. Right intensity scale bar corresponds to both PD-L1 PET images in Figure 3B.