Real-world side effects of targeted therapies: High-throughput association studies leveraging the CancerLinq Discovery lung cancer database.

1553 Background: Targeted therapies have unique side effect profiles distinct from other cancer drugs. Challenges of collecting generalizable toxicity data on these medications include the self-reporting infrastructure of existing post-market surveillance databases, as well as the infrequent use of many of these drugs by single cancer centers. The CancerLinQ Discovery (CLQD) database synthesizes deidentified electronic health record (EHR) data from millions of U.S. cancer patients. Diagnosis codes in this database can be used to study treatment side effects. Methods: We developed high-precision phenotyping algorithms to identify non-small cell lung cancer (NSCLC) patients receiving targeted therapies in the CLQD database. We then performed phenome-wide association studies (PheWAS) comparing new diagnosis codes in patients receiving each targeted therapy to new codes in patients receiving chemotherapy or immunotherapy. Codes with significant associations were compared to toxicity data reported in clinical trials and the FDA Adverse Event Reporting System (FAERS) database. Results: We identified 5,278 NSCLC patients who received targeted therapies with the latest CLQD data pull in 2022. For each of the 18 targeted therapies with five or more patients in the database, descriptive statistics and two PheWAS analyses are reported: one for diagnosis codes relative to chemotherapy, and one relative to immunotherapy. These analyses identified significant associations corresponding to known toxicity profiles as well as potentially underreported side effects. Conclusions: This high-throughput framework augments the characterization of side effect profiles for existing targeted therapies and can proactively monitor for toxicity signals as novel therapies and treatment indications emerge. The importance of collecting real-world data across institutions is highlighted in the ability to find clinically relevant associations even in targeted therapies directed against rare mutations. PheWAS analysis sample for side effects of osimertinib and capmatinib. Drug Control Side Effect Code p-value OR Osimertinib IO Abnormal EKG 3.68E-14* 2.91 Dermatitis 1.91E-09* 1.98 Disorders of muscle 8.18E-06* 2.13 Other CNS disorders 2.41E-05* 2.17 Thrombosis 2.90E-05* 1.49 Chemo Dermatitis 1.42E-62* 7.90 Skin symptoms 5.00E-45* 3.70 Abnormal EKG 3.95E-33* 4.93 Other musculoskeletal symptoms 5.61E-27* 6.14 Joint pains 1.09E-22* 2.43 Capmatinib IO Edema 2.34E-08* 4.19 Other soft tissue disorders 9.93E-05* 3.81 Hypocalcemia 1.06E-02 3.82 Pleural effusion 1.96E-02 2.22 Abnormal LFT results 4.97E-02 3.24 Chemo Edema 2.05E-14* 7.03 Other soft tissue disorders 1.75E-11* 10.10 Respiratory failure 4.20E-08* 7.12 Abnormal LFT results 3.12E-04* 8.70 Stroke 1.48E-03 6.68 <jats:p content-type="mtgabstrac