Cancer immunotherapy, or the utilization of the body's immune system to attack tumor cells, has gained prominence over the past few decades as a viable cancer treatment strategy. Recently approved immunotherapeutics have conferred remission upon patients with previously bleak outcomes and have expanded the number of tools available to treat cancer. Nanoparticles -including polymeric, liposomal, and metallic formulations - naturally traffic to the spleen and lymph organs and the relevant immune cells therein, making them good candidates for delivery of immunotherapeutic agents. Metallic nanoparticle formulations in particular are advantageous because of their potential for dense surface functionalization and their capability for optical or heat based therapeutic methods. Many research groups have investigated the potential of nanoparticle-mediated delivery platforms to improve the efficacy of immunotherapies. Despite the significant preclinical successes demonstrated by many of these platforms over the last twenty years, few metallic nanoparticles have successfully entered clinical trials with none achieving FDA approval for cancer therapy. In this review, we will discuss preclinical research and clinical trials involving metallic nanoparticles (MNPs) for cancer immunotherapy applications and discuss the potential for clinical translation of MNPs.

To compare US Food and Drug Administration (FDA) and European Medicines Agency (EMA) labeling for evidence based on patient-reported outcomes (PROs) of new oncology treatments approved by both agencies. Methods: Oncology drugs and indications approved between 2012 and 2016 by both the FDA and the EMA were identified. PRO-related language and analysis reported in US product labels and drug approval packages and EMA summaries of product characteristics were compared for each indication. Results: In total, 49 oncology drugs were approved for a total of 64 indications. Of the 64 indications, 45 (70.3%) included PRO data in either regulatory submission. No FDA PRO labeling was identified. PRO language was included in the summary of product characteristics for 21 (46.7%) of 45 indications. European Organisation for Research and Treatment of Cancer and Functional Assessment of Cancer Therapy measures were used frequently in submissions. FDA's comments suggest that aspects of study design (eg, open labels) or the validity of PRO measures was the primary reason for the lack of labeling based on PRO endpoints. Both agencies identified missing PRO data as problematic for interpretation. Conclusions: During this time period, the FDA and the EMA used different evidentiary standards to assess PRO data from oncology studies, with the EMA more likely to accept data from open-label studies and broad concepts such as health-related quality of life. An understanding of the key differences between the agencies may guide sponsor PRO strategy when pursuing labeling. Patient-focused proximal concepts are more likely than distal concepts to receive positive reviews.

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The EMA is more likely than the FDA to grant PRO claims and for higher order constructs. On a macro level, there appears to be poor concordance between claims granted by both agencies. On close examination, however, there appears to be greater concordance than previously recognized, which may be instructive in formulating future PRO strategies. Further research to create strategic alignment across agencies may be beneficial.