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. 2020 Jan;179(1):161-171.
doi: 10.1007/s10549-019-05453-z. Epub 2019 Oct 11.

A pooled analysis of the cardiac events in the trastuzumab adjuvant trials

Evandro de Azambuja  1 , Noam Ponde  2   3 , Marion Procter  4 , Priya Rastogi  5 , Reena S Cecchini  6 , Matteo Lambertini  2   7 , Karla Ballman  6 , Alvaro Moreno Aspitia  8 , Dimitrios Zardavas  9 , Lise Roca  10 , Richard D Gelber  11 , Martine Piccart-Gebhart  2   9 , Thomas Suter  12
Affiliations

A pooled analysis of the cardiac events in the trastuzumab adjuvant trials

Evandro de Azambuja et al. Breast Cancer Res Treat. 2020 Jan.

Abstract

Background: Trastuzumab-associated cardiotoxicity remains an issue for patients with HER2-positive breast cancer. This pooled analysis of 3 adjuvant trials investigated the incidence, timing, impact on treatment completion, and risk factors for trastuzumab-associated cardiotoxicity.

Methods: This is an individual patient data level pooled analysis of HERA, NSBAP B-31, and NCCTG 9831 (Alliance Trials). Definitions of cardiac events were as per each individual study.

Results: A total of 7445 patients enrolled in the 3 trials were included in the analysis, of which 4017 were in the trastuzumab and 3428 in the control (observation) arms, respectively. Median follow-up exceeded 10 years (119.2-137.2 months). Nearly all patients (97.4%) in the trastuzumab arms received anthracycline-based chemotherapy. In total, 452 patients in the trastuzumab arms experienced a cardiac event (11.3%), with most being mildly symptomatic or asymptomatic left ventricular ejection fraction (LVEF) decrease (351 patients, 8.7%). Severe congestive heart failure was more common in the trastuzumab arm (2.3%) than in the control arm (0.8%). Most cardiac events occurred during trastuzumab treatment (78.1%) and cardiac events were the main cause of discontinuation across the sample (10.0%); nevertheless, a large majority of patients completed trastuzumab treatment (76.2%). Baseline risk factors that were significantly associated with the development of cardiac events were baseline LVEF < 60%, hypertension, body mass index > 25, age ≥ 60 and, non-Caucasian ethnicity.

Conclusion: One year of trastuzumab increases the risk of cardiac events, though most consist of asymptomatic or mildly symptomatic LVEF drops. Adjuvant trastuzumab should be considered a safe treatment from a cardiac standpoint for most patients. Trastuzumab-associated cardiotoxicity is the main cause of discontinuation and further research is needed to individualize prevention and management.

Keywords: Breast cancer; Cardiotoxicity; LVEF; Trastuzumab.

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Conflict of interest statement

Conflict of Interest

Evandro de Azambuja has received honoraria and advisory board from Roche/GNE and Seattle Genetics; travel grants from Roche/GNE and GSK/Novartis and research grants to his Institute: Roche/GNE; Astra-Zeneca, GSK/Novartis, Servier

Noam Pondé has received honoraria from AZ and Eli Lilly and travel grants Eli Lilly and Novartis.

Marion Procter has declared that her institution received funding from Roche in respect to the APHINITY trial.

Matteo Lambertini has received honoraria Therame and consulting fee from TEVA

Pryia Rastogi has received travel and accommodations supported by Lilly, AZ, and GNE/Roche

Martine Piccart has declared board Member (Scientific Board) : Oncolytics, Radius; consultant (honoraria) : AstraZeneca, Camel-IDS, Crescendo Biologics, Debiopharm, G1 Therapeutics, Genentech, Huya, Immunomedics, Lilly, Menarini, MSD, Novartis, Odonate, Periphagen, Pfizer, Roche, Seattle Genetics; research grants to her Institute: AstraZeneca, Lilly, MSD, Novartis, Pfizer, Radius, Roche-Genentech, Servier, Synthon

Thomas Suter has declared research Support from Novartis and Amgen; consultant from Pfizer and advisory Board from Alnylam

Richard D Gelber declares that his institution receives support for his salary from Roche, AstraZeneca, Merck, Novartis, Ipsen, Celgene, Pfizer, and Ferring.

Dimitrios Zardavas has declared employment from BMS

Karla V. Ballman has declared consulting or Advisory Role from ARIAD; Medtronic; Takeda; Agenus; Patents, Royalties, Other Intellectual Property: Prostate cancer signature patent (Inst); Expert Testimony - Janssen Oncology; Lilly

Lise Roca, Alvaro Moreno Aspitia and Reena Cecchini have no conflict of interest to declare

Figures

Figure 1:
Figure 1:
cumulative incidence plot of any cardiac events in the Trastuzumab combined arm based on competing risks
Figure 2A:
Figure 2A:
plot of mean LVEF value over time up to month 18
Figure 2B:
Figure 2B:
plot of mean LVEF value over time up to month 36
See this image and copyright information in PMC

Comment in

References

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