BACKGROUND:Trastuzumab has greatly improved outcomes in patients with human epidermal growth factor receptor 2-positive breast cancer. To reduce costs and increase access, biosimilar products were approved after trials demonstrated short-term safety similar to that of reference trastuzumab. However, real-world data on cardiac safety are limited. OBJECTIVES:We evaluated the adoption of biosimilar trastuzumab and compared heart failure (HF) risk between users of reference and biosimilar trastuzumab. METHODS:Patients aged ≥18 years with breast cancer who received trastuzumab from 2018 to 2024 were identified in the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent surgery within the first year after cancer diagnosis were selected as a proxy for early-stage disease. Healthcare Common Procedure Coding System Level II codes were used to identify reference and biosimilar trastuzumab use, and International Classification of Diseases codes were used to identify HF diagnoses. Patients with an HF diagnosis before breast cancer surgery were excluded. Multivariable cause-specific Cox proportional hazards regression was used to examine the association of reference vs biosimilar trastuzumab use with HF risk. RESULTS:Among 5,135 patients identified, 43.9% received reference trastuzumab. Use of biosimilar trastuzumab increased from 0% in 2018 to 71.3% in 2024 (P < 0.001). The overall rate of HF was 5.9% (5.5% among reference trastuzumab users vs 6.3% among biosimilar trastuzumab users; P = 0.26). In multivariable analysis, there was no statistically significant difference in HF risk between patients treated with biosimilar trastuzumab and those treated with reference trastuzumab (adjusted HR [aHR]: 1.16; 95% CI: 0.92-1.46). Patients with a Charlson Comorbidity Index score ≥2 had a higher risk of HF than those with a score of 0 (aHR: 1.52; 95% CI: 1.11-2.08). Compared with patients aged 18 to 54 years, those aged 65 to 74 years (aHR: 1.61; 95% CI: 1.19-2.19) and ≥75 years (aHR: 1.95; 95% CI: 1.29-2.96) had a higher risk of HF. CONCLUSIONS:As biosimilar trastuzumab use continues to increase, our findings provide reassurance regarding its cardiac safety in the management of early-stage human epidermal growth factor receptor 2 breast cancer. Additional studies with longer follow-up are needed to confirm these findings and evaluate long-term cardiac outcomes.
Background RADICAL PC-2 (RAndomizeD Intervention for CArdiovascular and Lifestyle Risk Factors in Prostate Cancer Patients) was a pragmatic randomized controlled trial that tested whether routine referral to a cardiologist or an internist for cardiovascular (CV) risk-factor and lifestyle modification improves outcomes in patients with prostate cancer or receiving androgen-deprivation therapy. The intervention group had more favorable outcomes overall, driven by improved cholesterol control, with no differences in rates of CV death, myocardial infarction (MI), stroke, or heart failure (HF). Objectives The authors aim to identify patient subgroups more likely to benefit from routine CV care referral. Methods Prespecified subgroup analyses were used to assess whether patients at higher CV risk derived greater benefit from specialist referral, with treatment-effect heterogeneity assessed using interaction tests. The first primary outcome was a hierarchical composite of CV death, MI, stroke, HF, suboptimal cholesterol, and systolic blood pressure (SBP) control, evaluated using the win ratio. The second primary outcome was time to CV death, MI, stroke, or HF. Results Among 2487 participants, treatment effect differed by baseline total cholesterol ≤4 mmol/L vs >4 mmol/L (interaction P = 0.016), with respective win ratios of 1.21 (95% CI: 0.89-1.64) and 1.75 (95% CI: 1.51-2.03), and by baseline BP status (SBP ≥130 mm Hg or diastolic BP ≥80 mm Hg vs BP <130/80 mm Hg; interaction P = 0.003), with respective subdistribution HRs (sHRs) for CV death, MI, stroke, or HF of 0.86 (95% CI: 0.61-1.21) and 4.85 (95% CI: 1.65-14.26). The interaction for diabetes did not reach statistical significance (interaction P = 0.054) although the intervention effect estimates suggested a potential difference by diabetes status, with sHRs of 0.53 (95% CI: 0.24-1.15) among participants with diabetes and 1.25 (95% CI: 0.88-1.78) among participants without diabetes. The win ratio was higher among participants with total cholesterol >4 mmol/L, and sHRs were numerically lower among those with SBP ≥130 mm Hg or diastolic BP ≥80 mm Hg and diabetes. Conclusions Uncontrolled modifiable CV risk factors may identify patients with prostate cancer who are more likely to benefit from routine CV care referral.
