Cumulative incidence of cardiovascular events under tamoxifen and letrozole alone and in sequence: a report from the BIG 1-98 trial
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Background: Compared to tamoxifen, adjuvant treatment with aromatase inhibitors improves disease outcomes of postmenopausal women with hormone receptor-positive early breast cancer. In the international, randomized, double-blind BIG 1-98 trial, 8010 women were randomized to receive tamoxifen, letrozole, or sequential use of the agents for 5 years. With a focus on switching between agents, we investigated cardiovascular events over the entire 5-year treatment period. Methods: Of the 6182 patients enrolled, 6144 started trial treatment and were included in this analysis. Adverse events occurring during study treatment until 30 days after cessation were considered. Eight cardiovascular event types were defined. Cumulative incidence of events were estimated using the Kaplan–Meier method, without consideration for competing events. Multivariable Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI) for pairwise comparisons of treatment arms. Results: While on study treatment, 6.5% of patients (n = 397) had any cardiac events reported; for 2.4%, the event was grades 3–5, of which 11 (0.2%) were grade 5. Letrozole monotherapy was associated with higher risk of grade 1–5 ischemic heart disease (HR = 1.81; 95% CI, 1.06–3.08) compared with tamoxifen monotherapy. Patients assigned sequential tamoxifen →letrozole (HR = 1.59; 95% CI, 0.92–2.74) or sequential letrozole → tamoxifen (HR = 1.20; 95% CI, 0.68–2.14) showed a lesser degree of risk elevation. Patients assigned to tamoxifen-containing regimens had significantly higher risk of grade 1–5 thromboembolic events (tamoxifen monotherapy HR = 2.10; 95% CI, 1.42–3.12; tamoxifen → letrozole HR = 1.96; 95% CI, 1.32–2.92; letrozole → tamoxifen HR = 1.56; 95% CI 1.03–2.35) as compared with patients assigned letrozole alone. Conclusion: When initiating or switching between adjuvant endocrine treatments in postmenopausal patients, age and medical history, with special attention to prior cardiovascular events, should be balanced with expected benefit of the treatment.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Breast Cancer Research and Treatment |
| Vol/bind | 185 |
| Udgave nummer | 3 |
| Sider (fra-til) | 697-707 |
| Antal sider | 11 |
| ISSN | 0167-6806 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
The BIG 1-98 trial was financed by Novartis and coordinated by the International Breast Cancer IBCSG. Other support for the IBCSG was provided by The Swedish Cancer Society, The Swedish Research Council, The Cancer Council Australia, Australia New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research (SAKK), Cancer Research Switzerland, Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). Acknowledgements
Funding Information:
Manuela Rabaglio declares that she has no conflict of interest. Zhuoxin Sun declares that she has no conflict of interest. Rudolf Maibach declares that he has no conflict of interest. Anita Giobbie-Hurder reports that her institution receives support for her salary from nine National Institutes of Health (NIH) grants, including 5R01 CA193970-05, 1U24 CA224316-01, 1U24 CA224331-01, 5R01 CA229851-03, 5R01 CA190838-04, 5R01 CA221874-03, 1R01 CA244975-01, 1R01 CA252312-01, and 1R01 CA251599-01 in addition two other grants from the Susan Smith Center for Women’s Cancer and the Melanoma Research Alliance. Bent Ejlertsen reports that his institution receives research funding from AstraZeneca, Nanostring Technologies, Novartis, Pfizer, Roche, Samsung, and Venture Oncology. Vernon J. Harvey declares that he has no conflict of interest. Patrick Neven declares that he has no conflict of interest. István Láng declares that he has no conflict of interest. Hervé Bonnefoi declares that he has no conflict of interest. Andrew Wardley declares that he has no conflict of interest. Barbara Ruepp declares that she has no conflict of interest. Monica Castiglione declares that she has no conflict of interest. Alan S. Coates declares that he has no conflict of interest. Richard D. Gelber reports that his institution receives partial support for his salary from AstraZeneca, Celgene, Ferring, Ipsen, Merck, Novartis, Pfizer, and Roche. Marco Colleoni reports that he receives an honorarium from Novartis. Beat Thürlimann receives consultation fees from Amgen, AstraZeneca, Eli Lilly, Roche, and Pfizer, owns stocks in Novartis and Roche, holds leadership roles at the Swiss Cancer Research Foundation, Rising Tide for Clinical Cancer Research Foundation, Swiss Society of Senology Board of Directors, IBCSG Scientific Committee, IBCSG Biology Project Working Group, Cancer League of Eastern Switzerland Board of Directors, Swiss Foundation for Clinical Cancer Research Executive Committee, and is the Former SAKK President. Meredith M. Regan receives research funding (to the institution) from Novartis, Pfizer, Ipsen, TerSera, Merck, Ferring, Pierre Fabre, Roche, AstraZeneca, Bayer, and Bristol-Myers Squibb and receives consulting/advisory fees from Ipsen/Debiopharm (institution IBCSG), Bristol-Myers Squibb, and Tolmar Pharmaceuticals.
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