Key result
Adjuvant trastuzumab for early breast cancer was associated with an increased risk of symptomatic cardiac events during the first year (HR 9.96), but not over the entire follow-up (HR 1.41; 95% CI 0.99-2.02).
Why the study?
Clinical trials may underestimate toxicities in older patients with comorbidities and lack extended follow-up, leaving real-world acute and long-term symptomatic cardiac events after adjuvant trastuzumab unclear.
Does adjuvant trastuzumab increase the risk of symptomatic cardiac events compared to chemotherapy alone in patients with early breast cancer?
Cohort (n=8,427)
Does adjuvant trastuzumab increase the risk of symptomatic cardiac events compared to chemotherapy alone in patients with early breast cancer?
In real-world practice, symptomatic cardiac events associated with adjuvant trastuzumab are infrequent, occur early, and the excess risk disappears after one year of treatment.
Answers are grounded in this paper and cite their sources.
May warrant early cardiac monitoring with adjuvant trastuzumab; leaves open long-term risk in broader real-world populations.
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. 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.
No takes yet. Share an insight, caveat, or question.
Cosimo et al. (2019) conducted a cohort in early breast cancer (n=8,427). Adjuvant trastuzumab vs. Chemotherapy only was evaluated on Symptomatic cardiac events (heart failure and cardiomyopathy) (HR 1.41, 95% CI 0.99-2.02). Adjuvant trastuzumab for early breast cancer was associated with an increased risk of symptomatic cardiac events during the first year (HR 9.96), but not over the entire follow-up (HR 1.41; 95% CI 0.99-2.02).
Synapse has enriched 10 related papers. Consider them for comparative context: