Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

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.     

Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation

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Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

ObjectivesOlder adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake.Materials and MethodsWe conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005–2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis.ResultsOur study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%).ConclusionMore than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.     

Response to Rady re: Religion and Neuroscience

Neurocritical Care -