1872 - Long term follow-up (F/U) report of symptomatic cardiac events (SCEs) in 2,809 breast cancer (BC) patients (pts) treated with adjuvant trastuzumab (T) in real world (RW) practice

Background

Clinical trials, focusing on selected pts, may have underestimated toxicities in cases with advanced age and co-morbidities, that are common in RW practice. Furthermore, clinical trials do not provide extended F/U. Thus, we assessed acute and long-term SCEs after adjuvant T in a large/unselected BC pt population.

Methods

Using healthcare administrative database, ie clinical discharge records and drug prescriptions of the Lombardy region (Italy), we selected pts newly diagnosed with early BC between 01/2008 and 12/2011 and monitored until 12/2016. Pts treated with T were 1:2 matched with pts treated with chemotherapy only for age, date of treatment, and cardiovascular risk factors. SCEs included heart failure and cardiomyopathy based on ICD9-CM codes. The cumulative risk of SCEs was estimated using the Kaplan-Meier method; independent predictors were assessed by the Cox regression model.

Results

Of a cohort of 34,218 pts with incident BC, 2,809 pts treated with T were matched to 5,618 pts treated with chemotherapy only. One SCE during F/U was experienced in 52 (1.8%) of T-users and 88 (0.26%) of non-T users. No cardiac death occurred. The 1-year cumulative risk of SCEs was 0.96%, with 1/4 of SCEs occurring within the first 6 months, in T-users, and 0.16% in non T-users. However, the T-user excess risk disappeared after 1 year of T. Thus, the hazard ratio [HR] was 9.96 (95%CI 3-78-26.2) during the first year, and 1.41 (95%CI 0.99-2.02) during the entire F/U period. HR was higher in the elderly, age>70 years, 8.77 (95%CI 5.25-14.64), and in pts with at least one pre-existing CRFs 2.32 (95%CI 1.68-3.22).

Conclusions

In RW practice, SCEs during/after T are infrequent, early and self-limiting. Based on the timeline of SCEs, it might be unnecessary to monitor cardiac toxicity beyond the period of T treatment. Besides, to reduce the excess of cardiac risk of the first year, strategies including shortening T exposure or increasing the number of check-ups in asymptomatic pts should be accompanied by the development of biomarker(s) able to identify pts at risk before/immediately after T initiation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Serena Di Cosimo.

Funding

Associazione Italiana per la Ricerca sul Cancro (AIRC).

Disclosure

S. Di Cosimo: Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Teva; Advisory / Consultancy: EpiOnpharma; Advisory / Consultancy: Bayer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: GSK; Travel / Accommodation / Expenses: Celgene. All other authors have declared no conflicts of interest.