Better biomarkers are needed to predict treatment outcome in non-small cell lung cancer (NSCLC) patients treated with anti-programmed death1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint... Show moreBetter biomarkers are needed to predict treatment outcome in non-small cell lung cancer (NSCLC) patients treated with anti-programmed death1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint inhibitors. PD-L1 immunohistochemistry has limited predictive value, possibly because of tumor heterogeneity of PD-L1 expression. Noninvasive PD-L1 imaging using Zr-89-durvalumab might better reflect tumor PD-L1 expression. Methods: NSCLC patients eligible for second-line immunotherapy were enrolled. Patients received 2 injections of Zr-89-durvalumab: one without a preceding dose of unlabeled durvalumab (tracer dose only) and one with a preceding dose of 750 mg of durvalumab, directly before tracer injection. Up to 4 PET/CT scans were obtained after tracer injection. After imaging acquisition, patients were treated with 750 mg of durvalumab every 2 wk. Tracer biodistribution and tumor uptake were visually assessed and quantified as SUV, and both imaging acquisitions were compared. Tumor tracer uptake was correlated with PD-L1 expression and clinical outcome, defined as response to durvalumab treatment. Results: Thirteen patients were included, and 10 completed all scheduled PET scans. No tracer-related adverse events were observed, and all patients started durvalumab treatment. Biodistribution analysis showed Zr-89-durvalumab accumulation in the blood pool, liver, and spleen. Serial imaging showed that image acquisition 120 h after injection delivered the best tumor-to-blood pool ratio. Most tumor lesions were visualized with the tracer dose only versus the coinjection imaging acquisition (25% vs. 13.5% of all lesions). Uptake heterogeneity was observed within (SUVpeak range, 0.2-15.1) and between patients. Tumor uptake was higher in patients with treatment response or stable disease than in patients with disease progression according to RECIST 1.1. However, this difference was not statistically significant (median SUVpeak , 4.9 vs. 2.4; P = 0.06). SUVpeak correlated better with the combined tumor and immune cell PD-L1 score than with PD-L1 expression on tumor cells, although neither was statistically significant (P = 0.06 and P = 0.93, respectively). Conclusion: Zr-89-durvalumab was safe, without any tracer-related adverse events, and more tumor lesions were visualized using the tracer dose-only imaging acquisition. Zr-89-durvalumab tumor uptake was higher in patients with a response to durvalumab treatment but did not correlate with tumor PD-L1 immunohistochemistry. Show less
