ABSTRACT
Background: Pembrolizumab as an immune checkpoint inhibitor (ICI) has emerged as an effective treatment for many cancers. It has unique immune-related adverse events (irAE) and little is known about its risk of fatal adverse events (FAEs). We conducted a meta-analysis of clinical trials to determine the incidence and risk of FAEs with pembrolizumab.Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases including PUBMED and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models.Results: A total of 11 clinical trials with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%). The incidence of FAE significantly varied among different tumor types (p = .02), ranging from 0.2% in melanoma to 3.1% in breast cancer, and with its combination with chemotherapy (0.7%, 95% CI: 0.4-1.2% versus 7.0%, 95% CI: 4.9-10%; p<.01). Chemotherapy plus pembrolizumab 7.0% (95%CI: 4.9-10) as compared to pembrolizumab alone 0.7%, (95% CI: 0.4-1.2; p < .001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR = 1.24 (95% CI: 0.8-1.89; p = .31). The most common FAEs were due to infectious complication (26.5%), cardiac toxicity (14.7%) and pneumonitis (13.2%).Conclusions: The risk of FAEs with pembrolizumab may be similar to chemotherapy in cancer patients and may vary with tumor types and its combination with chemotherapy.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Clinical Trials as Topic/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions/etiology , Neoplasms/drug therapy , Drug-Related Side Effects and Adverse Reactions/diagnosis , Drug-Related Side Effects and Adverse Reactions/epidemiology , Humans , Incidence , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk FactorsABSTRACT
Pancreatic cancer accounts for approximately 3% of all cancers in US, and is the fourth leading cause of mortality in both men and women. It is a silent killer due to lack of early symptoms and the majority of patients present at advanced stage at the time of initial diagnosis. Only 15-20% of patients are candidates for curative resection and even then, the 5-year survival rates range from 10-25%. Despite recent advances in the treatment of advanced pancreatic cancer, the prognosis remains grim with 5-year overall survival (OS) of approximately 10%. Early detection is key for improving patient outcomes in this lethal disease. Contributing to the difficulty in the diagnosis and management is the anatomic location of the pancreas within the abdomen (retroperitoneal location and being adjacent to hollow viscus, solid organs and major vessels), and suboptimal response to systemic chemotherapy. Multimodality imaging (pancreatic protocol CT and MRI/MRCP) is often used for the diagnosis and staging of pancreatic adenocarcinoma. Interventional endoscopy is a relatively new field, and with Endoscopic techniques becoming more advanced, their role in diagnosis and management of pancreatic cancer is expanding rapidly. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the two main modalities used in cases of pancreatic neoplasms.
