Impact of bolus versus continuous infusion of doxorubicin (DOX) on cardiotoxicity in patients with breast cancer (BC) and sarcomas: Analysis of real-world data.

e19123 Background: Doxorubicin continues to play a central role in management of breast cancer and sarcomas. Dose-dependent cardiomyopathy is a challenge in its use. Strategies have been proposed to mitigate this, including administration by continuous intravenous (CIV) infusion as an alternative to bolus (BOL) administration. This study used real world data to explore the impact of DOX administration mode on cardiotoxicity, duration of DOX and time to treatment failure (TTF). Methods: This study used IBM MarketScan claims to identify patients age ≥ 18 who received at least 2 DOX administrations after cancer diagnosis. Patients with history of cardiac events/toxicities were excluded. Cardiac events were compared for BOL versus CIV overall, by tumor site and by regimen during three follow-up periods, early (within 1 year), middle (>1 to 5 years) and late (>5 years), from DOX initiation using Fisher’s exact test. Duration of DOX and TTF, defined as time from initiation of DOX to subsequent systemic therapy, hospice or death, were evaluated using Kaplan-Meier method and unadjusted Cox proportional hazards models. Results: 62,597 patients were eligible, including 38,961 with BC and 1,772 with sarcoma. Most patients had codes for both modes; 1,941 and 7,094 patients had exclusive BOL and CIV codes, respectively. For these patients, mean duration of DOX was longer for BOL vs. CIV (83.9 vs. 65.4 days, p<0.001). Cardiac events for BOL vs. CIV were 6.5% vs. 5.6% (p=0.098) during the early period, 4% vs. 5.1% (p=0.046) middle period, and 0.5% vs. 0.9% (p=0.068) late period. This pattern was consistent for BC and sarcoma and among those who were pre-treated. There were no differences in cardiac events for BOL vs. CIV for the chemotherapy naïve or DOX monotherapy groups (all periods p>0.10) but statistically different for the breast during the middle period, sarcoma at any time, and pretreated subgroup middle period (all p<0.05). TTF favored CIV over BOL among patients with BC (p<0.0001) but BOL over CIV in sarcoma (p=0.002). TTF was not significantly different between BOL and CIV for BC monotherapy (p=0.067) but was significant for sarcoma monotherapy favoring BOL administration (hazard ratio 0.72, 95% confidence interval 0.54-0.95, p=0.02). Conclusions: These data suggest that cardiac events may occur at a similar rate irrespective of mode of DOX administration. Further analyses are needed to understand how these relationships are impacted by other potential risk covariates (eg, age, gender) and by protective factors (eg, dexrazoxane).