⁸⁹Zr-DFO-Durvalumab PET/CT Before Durvalumab Treatment in Patients with Recurrent or Metastatic Head and Neck Cancer

Abstract

In this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed ⁸⁹Zr-DFO-durvalumab (anti–PD-L1 [programmed death ligand 1]) PET/CT in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) before monotherapy durvalumab treatment. The primary aims were to assess safety and feasibility of ⁸⁹Zr-DFO-durvalumab PET imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate ⁸⁹Zr-DFO-durvalumab uptake to tumor PD-L1 expression, ¹⁸F-FDG uptake, and treatment response of individual lesions. <b>Methods:</b> In this prospective multicenter phase I–II study (NCT03829007), patients with incurable R/M SCCHN underwent baseline ¹⁸F-FDG PET and CT or MRI. Subsequently, PD-L1 PET imaging was performed 5 d after administration of 37 MBq of ⁸⁹Zr-DFO-durvalumab. To optimize imaging conditions, dose finding was performed in the first 14 patients. For all patients (<i>n</i> = 33), durvalumab treatment (1,500 mg/4 wk, intravenously) was started within 1 wk after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum, 24 mo). CT evaluation was assessed according to RECIST 1.1 every 8 wk. PD-L1 expression was determined by combined positive score on (archival) tumor tissue. ⁸⁹Zr-DFO-durvalumab uptake was measured in ¹⁸F-FDG–positive lesions, primary and secondary lymphoid organs, and blood pool. <b>Results:</b> In total, 33 patients with locoregional recurrent (<i>n</i> = 12) or metastatic SCCHN (<i>n</i> = 21) were enrolled. ⁸⁹Zr-DFO-durvalumab injection was safe. A dose of 10 mg of durvalumab resulted in highest tumor-to-blood ratios. After a median follow-up of 12.6 mo, overall response rate was 26%. The disease control rate at 16 wk was 48%, with a mean duration of 7.8 mo (range, 1.7–21.1). On a patient level, ⁸⁹Zr-DFO-durvalumab SUV_peak or tumor-to-blood ratio could not predict treatment response (hazard ratio, 1.5 [95% CI, 0.5–3.9; <i>P</i> = 0.45] and 1.3 [95% CI, 0.5–3.3; <i>P</i> = 0.60], respectively). Also, on a lesion level, ⁸⁹Zr-DFO-durvalumab SUV_peak showed no substantial correlation to treatment response (Spearman ρ, 0.45; <i>P</i> = 0.051). Lesional ⁸⁹Zr-DFO-durvalumab uptake did not correlate to PD-L1 combined positive score but did correlate to ¹⁸F-FDG SUV_peak (Spearman ρ, 0.391; <i>P</i> = 0.005). <b>Conclusion:</b> PINCH is the first, to our knowledge, PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of ⁸⁹Zr-DFO-durvalumab PET/CT in a multicenter trial. ⁸⁹Zr-DFO-durvalumab uptake did not correlate to durvalumab treatment response.