The Endocrine Treatment Landscape for Patients with HR+ HER2− Early-stage Breast Cancer in Germany Before the Introduction of CDK4/6 Inhibitor Therapy – A Real-World Analysis

Abstract

Introduction

While premenopausal patients with HR+ HER2− early breast cancer are treated with tamoxifen +/− ovarian suppression with a GnRH analog or an aromatase inhibitor (AI) + GnRH, the majority of postmenopausal women receive an AI due to its higher efficacy compared to tamoxifen. As the introduction of CDK4/6 inhibitors into the treatment of early-stage breast cancer with a higher risk of recurrence will probably result in a shift in the endocrine treatment landscape, the question is what treatment did potential candidates for CDK4/6 inhibitors in Germany receive before CDK4/6 inhibitors were available.

Patients and Methods

As part of a retrospective multicenter analysis, anonymized data were collected of patients with HR+ HER2− early-stage breast cancer who received endocrine therapy in the period between 10/2021 and 03/2022. Potential candidates for CDK4/6 inhibitor treatment were classified into different risk cohorts using the inclusion criteria of the NATALEE and monarchE trials.

Results

The data of 238 patients from 29 different centers were analyzed. While 20.6% of patients met the monarchE criteria, the subgroup which met the NATALEE inclusion criteria consisted of 46.2% of patients. 53.8% of patients did not meet the inclusion criteria for either the NATALEE or the monarchE trial. More than half of the patients did not receive chemotherapy. 28.6% of patients in the whole cohort were premenopausal. 67.6% of premenopausal women received neo-/adjuvant chemotherapy. 61.8% of premenopausal patients received tamoxifen as adjuvant endocrine therapy, 19.1% received an AI + GnRH and 10.3% were treated with tamoxifen + GnRH.

Conclusion

Despite the high percentage of premenopausal patients who received aggressive treatment in the form of chemotherapy, only one third of premenopausal patients received GnRH in addition to their standard endocrine therapy. Studies carried out at a later point in time and registry studies will be necessary to see how the endocrine therapy landscape in Germany has changed following the introduction of CDK4/6 inhibitors.

Keywords

breast cancer - endocrine treatment - OFS - tamoxifen - aromatase inhibitor

• References/Literatur

• 1 Ditsch N, Wocke A, Untch M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2022. Breast Care (Basel) 2022; 17: 403-420
• 2 Thomssen C, Balic M, Harbeck N. et al. St. Gallen/Vienna 2021: A Brief Summary of the Consensus Discussion on Customizing Therapies for Women with Early Breast Cancer. Breast Care (Basel) 2021; 16: 135-143
• 3 Paluch-Shimon S, Lueck H, Beith J. et al. 153P Adjuvant endocrine therapy combined with abemaciclib in monarchE patients with high-risk early breast cancer: Disease characteristics and endocrine therapy choice by menopausal status. Ann Oncol 2021; 32: S427-S428
• 4 Tarantino P. Consensus statement regarding use of adjuvant abemaciclib in patients with early-stage hormone-receptors positive breast cancer. Boston, MA: Dana-Farber Cancer Institute; 2021
• 5 Novartis. Novartis Kisqali® Phase III NATALEE trial meets primary endpoint at interim analysis demonstrating clinically meaningful benefit in broad population of patients with early breast cancer. 27.03.2023 Accessed March 27, 2023 at: https://www.novartis.com/news/media-releases/novartis-kisqali-phase-iii-natalee-trial-meets-primary-endpoint-interim-analysis-demonstrating-clinically-meaningful-benefit-broad-population-patients-early-breast-cancer
• 6 Tripathy D, Im SA, Colleoni M. et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 2018; 19: 904-915
• 7 ClinicalTrials.gov. Accessed December 01, 2022 at: https://clinicaltrials.gov/
• 8 Heer E, Harper A, Escandor N. et al. Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. Lancet Glob Health 2020; 8: e1027-e1037
• 9 Johnston SRD, Harbeck N, Hegg R. et al. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol 2020; 38: 3987-3998
• 10 Wockel A, Festl J, Stuber T. et al. Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2018; 78: 1056-1088
• 11 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
• 12 Pagani O, Francis PA, Fleming GF. et al. Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT. J Clin Oncol 2020; 38: 1293-1303
• 13 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol 2022; 23: 382-392
• 14 Pagani O, Walley BA, Fleming GF. et al. Adjuvant Exemestane With Ovarian Suppression in Premenopausal Breast Cancer: Long-Term Follow-Up of the Combined TEXT and SOFT Trials. J Clin Oncol 2023; 41: 1376-1382
• 15 Regan MM, Neven P, Giobbie-Hurder A. et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1–98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol 2011; 12: 1101-1108
• 16 Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
• 17 Baum M, Budzar AU, Cuzick J. et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002; 359: 2131-2139