PURPOSE: The rapidly rising costs of targeted oral anticancer medicines (TOAMs) raise concerns over their affordability. Our goal was to examine recent trends in the uptake of TOAMs among cancer patients with Medicare Part D, the share of TOAM users who reached catastrophic coverage, and the annual spending on TOAMs in the catastrophic phase. METHODS: Using the 5% SEER-Medicare, we included patients age 65 years and older who had one primary cancer diagnosis between 2011 and 2016. We included person-years where patients were enrolled in a Part D plan for the entire year, did not receive the low-income subsidy at any time of the year, and received anticancer systemic therapies. We estimated the trends in the share of patients who used TOAMs, the percentage of TOAM users reaching catastrophic coverage, and the total and patient out-of-pocket spending on TOAMs in the catastrophic phase in a year. RESULTS: From 2011 to 2016, the uptake of TOAMs among our study population increased from 3.6% to 8.9%. The percentage of non–low-income subsidy TOAM users who reached catastrophic coverage increased from 54.6% to 60.3%. Among those who reached the catastrophic phase, mean total gross spending on TOAMs in the catastrophic phase increased from $16,074 (USD) to $64,233 (USD) and mean patient out-of-pocket spending from $596 (USD) to $2,549 (USD). The mean 30-day total spending increased from $4,011 (USD) to $8,857 (USD), and the mean 30-day out-of-pocket spending from $154 (USD) to $328 (USD). CONCLUSION: The high and growing burden from TOAMs highlighted the need for reining in drug prices and capping out-of-pocket spending.