89Zr-DFO-durvalumab PET/CT prior to durvalumab treatment in patients with recurrent or metastatic head and neck cancer

Sarah Verhoeff, Pim P. van de Donk, Erik H. Aarntzen, Sjoukje F. Oosting, Adrienne H. Brouwers, IHC Miedema, J Voortman, C. W. Menke, R Boellaard, Dennis Vriens, Marije Slingerland, Rick Hermsen, Ilse A C H van Engen-van Grunsven, Sandra Heskamp, Carla M L van Herpen

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Background: In the PINCH study we performed 89Zr-DFO-durvalumab (anti-PD-L1) PET/CT in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) prior to 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. Methods: In this prospective multicenter phase I-II study (NCT03829007), patients with incurable R/M SCCHN underwent baseline [18F]FDG PET and CT or MRI imaging. Subsequently, PD-L1 PET-imaging was performed 5 days after 37MBq [89Zr]Zr-DFO-durvalumab administration. To optimize imaging conditions, dose-finding was performed in the first 14 patients. For all patients, durvalumab treatment (1500mg/4 weeks, IV) was started <1 week after PD-L1 PET imaging and continued until disease progression or unacceptable toxicity (maximum 24 months). CT evaluation was assessed according to RECIST 1.1 every 8 weeks. PD-L1-expression was determined by combined positive score (CPS) on (archival) tumor-tissue. [89Zr]Zr-DFO-durvalumab uptake was measured in [18F]FDG-positive lesions, primary and secondary lymphoid organs, and bloodpool. Results: In total, 33 patients with locoregional recurrent (n = 12) or metastatic SCCHN (n = 21) were enrolled. [89Zr]Zr-DFO-durvalumab injection was safe. A dose of 10mg durvalumab resulted in highest tumor-to-blood-ratios. After a median follow-up of 12.6 months, overall response rate was 26%. The disease control rate at 16 weeks was 48% with a mean duration of 7.8 months (range 1.7-21.1). On a patient level, [89Zr]Zr-DFO-durvalumab-SUVpeak or tumor-to-blood ratio could not predict treatment response (HR 1.4 (95%CI 0.5-3.9, P = 0.54) and (HR 1.3 (95%CI 0.5-3.6, P = 0.61) respectively). Also, on a lesion level, [89Zr]Zr-DFO-durvalumab-SUVpeak showed no substantial correlation to treatment response (Spearman ρ= 0.45, P = 0.051). Lesional [89Zr]Zr-DFO-durvalumab-uptake did not correlate to PD-L1 CPS score, but did correlate to [18F]FDG SUV peak (Spearman ρ= 0.391, P = 0.005). Conclusion: PINCH is the first PD-L1 PET/CT study in patients with R/M SCCHN and has shown the feasibility and safety of [89Zr]Zr-DFO-durvalumab PET/CT in a multi-center trial. [89Zr]Zr-DFO-durvalumab-uptake did not correlate to durvalumab treatment response.
Original languageEnglish
JournalJournal of Nuclear Medicine
Publication statusPublished - 5 May 2022

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