Big Data Analysis of Drug Induced Hypersensitivity and Anaphylaxis Reactions in Clinical Cancer Trials

RATIONALE: Cancer therapy is often associated with hypersensitivity reactions (HSRs) and anti-neoplastics are the third leading cause of fatal drug-induced anaphylaxis in the United States. Several classes of immunologic and chemotherapeutic agents have been associated with increases in hypersensitivity reactions including: platinum compounds, taxanes, L-asparaginase, epipodophyllotoxins, and procarbazine. However, little data exists on population level incidence of HSRs across cancer clinical trials.

METHODS: Clinical trial outcome data from approximately 18,000 studies from 2000-2014 were extracted from ClinicalTrials.gov. The dataset, which included study name, medical condition, intervention, arm titles, and adverse drug reactions, was queried for drug hypersensitivity reactions using the key terms: hypersensitivity, allergic reaction, allergy, anaphylaxis, allergic dermatitis, and drug hypersensitivity. Studies were sorted by condition; non-cancer studies and those with <10 participants were removed. Drug interventions, including both single and combination drug therapy, were categorized by drug class(es).

RESULTS: Preliminary population analysis of 425 of the 1605 qualifying clinical trials from this dataset revealed 3,013 adverse drug hypersensitivity reactions of 118,159 patients at risk for HSRs (2.5% incidence). 427 of these adverse events were categorized as anaphylaxis in the 10,430 patients at risk for these events (4% incidence). Anaphylactic events were the most common in cancer drug trial arms using antimetabolites or drug combinations. The most common drug combinations resulting in anaphylaxis were alkylating agent/platinum/plant alkaloid (incidence 11%), antimetabolite/chemoprotectant/monoclonal antibody/platinum (incidence 10%) and platinum/taxane/mTOR inhibitors (incidence 20%).

CONCLUSIONS: Our preliminary data suggests that antimetabolites may play a larger factor in hypersensitivity reactions in cancer chemotherapy than previously thought.