Real-World Analysis of Off-Label Use of Molecularly Targeted Therapy in a Large Academic Medical Center Cohort

The primary objective of this study is to quantify the use of off-label molecularly targeted therapy and describe the clinical situations in which off-label targeted therapy are used. A key secondary objective is to report the outcomes of patients treated with off-label use of targeted therapy.We searched the electronic health record between 2000 and 2020 at our center to characterize the volume, clinical settings, and outcomes associated with off-label use of targeted therapies in different types of solid tumors.Among 46,712 patients who received targeted therapies, we identified 119 instances of off-label use of targeted therapy. Colon cancer was the most common cancer type to receive off-label targeted therapy in 18 patients (15.1%), followed by 13 with non-small-cell lung cancer (10.9%), eight with cholangiocarcinoma (6.7%), and seven with glioblastoma (5.9%). The most frequent molecular rationale for off-label therapy came from a comprehensive next-generation sequencing test (53.7%). The most frequently mutated gene that provided the rationale for targeted therapy was BRAF (20.1%), with BRAFV600E being the most common molecular alteration overall (15.1%). The median duration of off-label targeted therapy was 3.58 months, and the overall survival of treated patients was 7.59 months. There were 37 patients (31.1%) treated for longer than 6 months, 23 patients (19.3%) who survived ≥ 2 years, and 13 patients who were still on therapy as of June 2020.In this large cohort study of patients with solid tumors, off-label use of targeted therapy was uncommon. With that said, a notable proportion of patients had treatment durations ≥ 6 months and survivals of ≥ 2 years.