<sup>89</sup>Zr-DFO-Durvalumab PET/CT Before Durvalumab Treatment in Patients with Recurrent or Metastatic Head and Neck Cancer
Sarah R. Verhoeff, Pim P. van de Donk, Erik H.J.G. Aarntzen, Sjoukje F. Oosting, Adrienne H. Brouwers, Iris H.C. Miedema, Jens Voortman, Willemien C. Menke-van der Houven van Oordt, Ronald Boellaard, Dennis Vriens, Marije Slingerland, Rick Hermsen, Ilse van Engen‐van Grunsven, Sandra Heskamp, Carla M.L. van Herpen
Abstract
In this PD-L1 ImagiNg to prediCt durvalumab treatment response in SCCHN (PINCH) study, we performed <sup>89</sup>Zr-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 <sup>89</sup>Zr-DFO-durvalumab PET imaging and predict disease control rate during durvalumab treatment. Secondary aims were to correlate <sup>89</sup>Zr-DFO-durvalumab uptake to tumor PD-L1 expression, <sup>18</sup>F-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 <sup>18</sup>F-FDG PET and CT or MRI. Subsequently, PD-L1 PET imaging was performed 5 d after administration of 37 MBq of <sup>89</sup>Zr-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. <sup>89</sup>Zr-DFO-durvalumab uptake was measured in <sup>18</sup>F-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. <sup>89</sup>Zr-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, <sup>89</sup>Zr-DFO-durvalumab SUV<sub>peak</sub> 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, <sup>89</sup>Zr-DFO-durvalumab SUV<sub>peak</sub> showed no substantial correlation to treatment response (Spearman ρ, 0.45; <i>P</i> = 0.051). Lesional <sup>89</sup>Zr-DFO-durvalumab uptake did not correlate to PD-L1 combined positive score but did correlate to <sup>18</sup>F-FDG SUV<sub>peak</sub> (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 <sup>89</sup>Zr-DFO-durvalumab PET/CT in a multicenter trial. <sup>89</sup>Zr-DFO-durvalumab uptake did not correlate to durvalumab treatment response.