Comparative Efficacy and Safety of Extended Adjuvant Endocrine Therapy for Hormone Receptor-positive Early Breast Cancer: a Bayesian Network Meta-analysis

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2023 Oct 3

PMID 37787817

Authors

Peng He

Jing Li

Minyan Chen

Meng Huang

Yibin Qiu

Qindong Cai

Yuxiang Lin

Chuan Wang

Fangmeng Fu

Affiliations

Soon will be listed here.

Abstract

Purpose: Optimal extended adjuvant endocrine therapy (ET) duration and strategy for hormone receptor-positive (HR +) early breast cancer remain unclear. In this network meta-analysis (NMA), the efficacy and safety of all available extended adjuvant ETs were compared and ranked.

Methods: PubMed, Embase, and Cochrane Library and abstracts presented at ASCO, SABCS, and ESMO were searched on March 5, 2022. Fourteen randomized controlled trials (RCTs) comprising eight extended adjuvant ETs for HR + breast cancer and 38,070 patients were analyzed. Main outcomes were disease-free survival (DFS), overall survival (OS), grade ≥ 3 adverse events (AEs), and contralateral breast cancer (CBC). Direct and indirect comparisons were integrated via Bayesian NMA. Hierarchical cluster analysis was performed to jointly rank efficacy and safety outcomes.

Results: Compared with that of 5 year ET, extended 10 year aromatase inhibitor (AI) treatment provided the greatest DFS benefit (HR = 0.45, 95%CrI 0.23-0.83), whereas no strategy differed significantly in terms of the other main outcomes. Extended 10 year AI treatment was the preferred strategy for DFS improvement and CBC prevention (surface under the cumulative ranking curve: 93.51% and 91.29% probability, respectively). All strategies had comparable safeties (grade ≥ 3 AEs). Compared with that of 5 year ET, 10 year extended AI significantly increased arthralgia (OR = 1.65, 95%CrI 1.02-2.93) and osteoporosis (OR = 3.33, 95%CrI 1.19-9.68).

Conclusion: Extended 10 year AI therapy may be optimal for HR + early breast cancer given its relatively high efficacy and safety.

References

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P . Breast cancer. Nat Rev Dis Primers. 2019; 5(1):66. DOI: 10.1038/s41572-019-0111-2. View

Hart C, Migliaccio I, Malorni L, Guarducci C, Biganzoli L, Di Leo A . Challenges in the management of advanced, ER-positive, HER2-negative breast cancer. Nat Rev Clin Oncol. 2015; 12(9):541-52. DOI: 10.1038/nrclinonc.2015.99. View

Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio I . Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019; 30(8):1194-1220. DOI: 10.1093/annonc/mdz173. View

Burstein H, Lacchetti C, Anderson H, Buchholz T, Davidson N, Gelmon K . Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol. 2018; 37(5):423-438. DOI: 10.1200/JCO.18.01160. View

Machin D, ANDERSEN K . Randomized trial of two versus five years of adjuvant tamoxifen for postmenopausal early stage breast cancer. J Natl Cancer Inst. 1997; 89(9):659-60. DOI: 10.1093/jnci/89.9.659. View

Pan H, Gray R, Braybrooke J, Davies C, Taylor C, McGale P . 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med. 2017; 377(19):1836-1846. PMC: 5734609. DOI: 10.1056/NEJMoa1701830. View

Loibl S, Furlanetto J . Integrating CDK4/6 inhibitors in the treatment of patients with early breast cancer. Breast. 2021; 62 Suppl 1:S70-S79. PMC: 9097805. DOI: 10.1016/j.breast.2021.12.008. View

Rossi L, McCartney A, De Santo I, Risi E, Moretti E, Malorni L . The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review. Cancer Treat Rev. 2019; 74:29-34. DOI: 10.1016/j.ctrv.2019.01.007. View

10.

Jakesz R, Greil R, Gnant M, Schmid M, Kwasny W, Kubista E . Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst. 2007; 99(24):1845-53. DOI: 10.1093/jnci/djm246. View

11.

Del Mastro L, Mansutti M, Bisagni G, Ponzone R, Durando A, Amaducci L . Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021; 22(10):1458-1467. DOI: 10.1016/S1470-2045(21)00352-1. View

12.

Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V . Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2012; 381(9869):805-16. PMC: 3596060. DOI: 10.1016/S0140-6736(12)61963-1. View

13.

Goss P, Ingle J, Martino S, Robert N, Muss H, Piccart M . Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst. 2005; 97(17):1262-71. DOI: 10.1093/jnci/dji250. View

14.

Goss P, Ingle J, Pritchard K, Robert N, Muss H, Gralow J . Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. N Engl J Med. 2016; 375(3):209-19. PMC: 5024713. DOI: 10.1056/NEJMoa1604700. View

15.

Gnant M, Fitzal F, Rinnerthaler G, Steger G, Greil-Ressler S, Balic M . Duration of Adjuvant Aromatase-Inhibitor Therapy in Postmenopausal Breast Cancer. N Engl J Med. 2021; 385(5):395-405. DOI: 10.1056/NEJMoa2104162. View

16.

Zdenkowski N, Forbes J, Boyle F, Kannourakis G, Gill P, Bayliss E . Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol. 2016; 27(5):806-12. DOI: 10.1093/annonc/mdw055. View

17.

Tjan-Heijnen V, van Hellemond I, Peer P, Swinkels A, Smorenburg C, van der Sangen M . Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol. 2017; 18(11):1502-1511. DOI: 10.1016/S1470-2045(17)30600-9. View

18.

Fisher B, Dignam J, Bryant J, Wolmark N . Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001; 93(9):684-90. DOI: 10.1093/jnci/93.9.684. View

19.

Jerusalem G, Farah S, Courtois A, Chirgwin J, Aebi S, Karlsson P . Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy. Ann Oncol. 2021; 32(10):1256-1266. DOI: 10.1016/j.annonc.2021.07.017. View

20.

Mamounas E, Jeong J, Wickerham D, Smith R, Ganz P, Land S . Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008; 26(12):1965-71. DOI: 10.1200/JCO.2007.14.0228. View