Abstract 198TiP
Background
Non-small cell lung cancer (NSCLC) accounts for 80–90% of all lung cancer cases, the leading cause of death by cancer worldwide. Fortunately, great advances in therapy have been achieved over those last years. Immune checkpoint inhibitors (ICI) are an example, having significantly changed prognosis in these patients, however not for all. Multiple biomarkers have been studied to stratify responders from non-responders. Detection of programmed cell death ligand-1 (PD-L1) expression in tissue biopsy is until now the most predictive. Even though, patients with the same value of PD-L1, even if high, may have different response to ICI which is a critical aspect in clinical approach. As tumoral heterogeneity is a known and determinant factor for therapy response, its accurate evaluation by immuno-PET may represent a valid and clinically useful strategy to help predict response to ICI. It may represent the first step to improve global NSCLC treatment strategy including overcoming of ineffective treatments in a disease that is known to be very aggressive and where the unique opportunity to best treat cannot be missed.
Trial design
This multicenter study will include the development of 89Zr-pembrolizumab PET at Nuclear Institute-ICNAS and usual care and imaging follow-up of patients with locally advanced or metastatic NSCLC with PD-L1 expression on tumor biopsy of ≥50% eligible for first-line pembrolizumab at Leiria Hospital Center and Coimbra Hospital and University Center. At baseline patients will be submitted to [18F] FDG-PET and immuno-PET. They will receive the combined dose of 2.5 mg pembrolizumab labeled with 37 MBq 89Zr-oxalate and 2.5 mg of unlabeled pembrolizumab and imaging will be carried out on day 7 after tracer injection. Neutrophil-lymphocyte ratio (NLR) will also be calculated. Treatment with pembrolizumab will be started within two weeks and usual care and imaging follow-up will be performed. Tumor response to pembrolizumab will be measured by objective response rate (iRECIST criteria). To determine whether immunoPET can help identify responders analyse will be performed by SUV lesion determination, [18F] FDG and 89Zr-pembrolizumab PET paired positive lesion determination and combination with NLR.
Legal entity responsible for the study
Faculty of Medicine of Coimbra University, Portugal.
Funding
Institute of Nuclear Sciences Applied to Health (ICNAS) of Coimbra University, Portugal.
Disclosure
All authors have declared no conflicts of interest.