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Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?
Authors:Liam Masterson  James Howard  Jazmina Gonzalez-Cruz  Christopher Jackson  Catherine Barnett  Lewis Overton  Howard Liu  Rahul Ladwa  Fiona Simpson  Margie McGrath  Ben Wallwork  Terry Jones  Christian Ottensmeier  Melvin LK Chua  Chris Perry  Rajiv Khanna  Benedict Panizza  Sandro Porceddu  Matt Lechner
Institution:1. Department of Head & Neck Oncology, Princess Alexandra Hospital, Brisbane, Australia;2. Diamantina Institute, University of Queensland, Woolloongabba, QLD, Australia;3. Department of Head & Neck Oncology, Princess Alexandra Hospital, Brisbane, Australia

Faculty of Medicine, University of Queensland, St. Lucia, Australia;4. Liverpool Head & Neck Centre, University of Liverpool, Liverpool, United Kingdom;5. Department of Medicine, University of Southampton, Southampton, UK;6. Divisions of Radiation Oncology & Medical Science, National Cancer Centre, Singapore, Singapore;7. QIMR Berghofer Medical Research Institute, Brisbane City, QLD, Australia;8. UCL Cancer Institute, University College London, London, United Kingdom

Abstract:Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.
Keywords:nasopharyngeal carcinoma  checkpoint inhibitors  clinical trials
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